Cell Bio 4

Adhesion to neighboring cells via cadherins mediates

"contract inhibition of growth"

Some Functions of PCD in Animal Development

(A and B) Sculpting. (C and D) Deleting unwanted structures. (E) Controlling cell numbers. (F and G) Eliminating nonfunctional, harmful, abnormal, or misplaced

A Werner's Syndrome patient

*******nn

Myostatin

-inhibits growth and proliferation of myoblasts (produces muscle cells

cancer stem cell

.....

Properties of transformed [cancer] cells

1. Lack of density dependent inhibition of cell growth 2. Reduced requirement for Growth Factors 3. Loss of contact inhibition 4. Alterations in the ECM and Cytoskeleton 5. Protease secretion especially metalloproteinases. 6. Secretion of growth factors promoting angiogenesis 7. Failure of normal differentiation 8. Failure to undergo Programmed cell death. [Apoptosis] 9. Transformed cell can cause tumors when injected into susceptible mice. 10. Transformed cells have glycoproteins and glycolipids in their plasma membranes making their membranes more fluid than normal cells. 11. Aneuploidy: Aberrant chromosome number. 12. Immunodeficiency 13. Failure of immunological surveillance. 14. Altered metabolism (Warburg Effect).

A single CDK (M-CDK) is responsible for bringing about the diverse rearrangements at the beginning of mitosis

1.Assembly of the mitotic spindle 2. Ensure chromosomes are atached to spindle 3. Chromosome condensation 4. Nuclear envelope breakdown 5. Actin cytoskeleton rearrangement 6. Reorganization of golgi and ER

Oncogenes can be classified into at least 6 classes

1.Growth factors 2.Growth factor receptors 3.Protein kinases or their activators including all Ras family members, 4.Cell cycle control proteins 5.Proteins regulating programmed cell death. [Apoptosis] 6.Transcription factors.

confluence

A gathering together in a state of contact inhibition

Oncogene

A gene that is a mutated (changed) form of a gene involved in normal cell growth. Oncogenes may cause the growth of cancer cells. Mutations in genes that become oncogenes can be inherited or caused by being exposed to substances in the environment that cause cancer.

Proto-Oncogene

A normal gene that, when mutated, can become and oncogene

G2/M DNA damage checkpoint

A protein kinase cascade stops the cell cycle until all DNA is replicated.

epistasis

A type of gene interaction in which one gene alters the phenotypic effects of another gene that is independently inherited.

Tumor suppressor

A type of gene that makes a protein called a tumor suppressor protein that helps control cell growth. Mutations (changes in DNA) in tumor suppressor genes may lead to cancer. Also called antioncogene

In G1 phase Cells exit from mitosis when

APC/C degrades the cyclins required for mitotic Cdk activity and cells either grow or enter a noncycling G0 phase

A protein (called geminin) inhibits assembly of prereplication complexes

APC/C destroys geminin during mitosis, allowing prereplication complexes to assemble in G1

PARP can be activated in cells experiencing stress and/or DNA damage

Activated PARP can deplete the ATP of a cell in an attempt to repair the damaged DNA. ATP depletion in a cell leads to lysis and cell death (necrosis). PARP also has the ability to induce programmed cell death, via the production of PAR, which stimulates mitochondria to release AIF.[11] This mechanism appears to be caspase-independent. Cleavage of Parp, by enzymes such as caspases or cathepsins, typically inactivate Parp. The size of the cleavage fragments can give insight into which enzyme was responsible for the cleavage, and can be useful in determining which cell death pathway has been activated.

During the G1 restriction point the Prerequisites for replicating the genome and continuing through the cell cycle are

Adequate cell size No DNA damage. There must be nutrients and growth factors.

Changes in the mitotic spindle during anaphase

Anaphase A: Kinetochore microtubules shorten, and motors associated with kinetochores pull the kinetochores toward the poles. Anaphase B: Bipolar kinesins interact with the overlapping, antiparallel interpolar microtubules to push the poles apart. Interpolar microtubules also elongate in some cells.

Cytokinesis

Beginning in metaphase and continuing through anaphase, a contractile ring of actin filaments, accessory proteins, and myosin-II assembles around the equator of the cell midway between the poles of the mitotic spindle. In telophase the contractile ring begins to constrict the equator around the remnants of the central spindle (mid-body). Fusion of the plasma membrane completes cell division

Mititotic Spindle structure during prometaphase

Bilaterally symmetrical: Radial arrays of microtubules emanate from both poles and interact with the chromosomes between the poles. Microtubules minus ends associate with the poles, and plus ends probe the surrounding area. Astral microtubules: Plus ends radiate out from each pole. Kinetochore microtubules: Kinetochores capture plus ends and reduce the chance of catastrophes; kinetochores of paired sister chromatids attach to microtubules from opposite spindle poles. Growth and shrinkage of kinetochore microtubules and the action of motors move the chromosomes to the mid-plane of the spindle. Interpolar microtubules: Plus ends overlap with microtubules from the opposite pole and are coupled to them by both plus end-directed kinesins and minus end-directed kinesins. Spindle structure is determined by the dynamics of the microtubules and the actions of at least seven kinesins and a dynein, which produce forces on microtubules and kinetochores.

Battling kinase and phosphatase activities regulate Cdk1/cyclin B

CAK kinase (Ckd7/cyclin H) phosphorylates Cdk1, opening the active site for substrate binding, but this does not turn on Cdk1/cyclin B, since Wee1 (and a related kinase myt1) phosphorylate inhibitory sites that hold the Cdk1/cyclin B kinase in check, Polo kinase (PlX1 in the illustration) activates Cdc25 phosphatase, Cdc25 phosphatase removes inhibitory phosphates from Cdk1, Cdk1/cyclin B also activates Cdc25 phosphatase, creating a positive feedback loop for Cdk1/cyclin B activation,

Two classes of protein inhibitors bind Cdks:

CKIs (cyclin-dependent kinase inhibitors) and INKs help to control Cdk activity in the G1 and G0 phases of the cell cycle.

Many Cancers may be treatable by enhancing the Immune Response against the specific

Cancer cells can tell T cells not to attack them. So we make drugs to stop that.

Prophase in detail with regards to chromosomal condensation

Changes in the nucleus that lead to chromosome condensation: Cdk1/cyclin B phosphorylates condensin, which promotes its accumulation in the nucleus. Cdk1/cyclin B and aurora B kinase also phosphorylate histones. Together active condensin and histone modifications promote condensation of each chromosome into a thread visible on light microscopy. Sister chromatids are paired from end-to-end by cohesin. The nucleolus disperses.

Prophase

Chromosomes condense in the nucleus, nucleolus disassembles, and duplicated centrosomes separate to opposite sides of the nucleus and organize the two poles of the mitotic spindle.

In metaphase

Chromosomes oscillate back and forth on the metaphase plate between the poles

Activation of APC/C leads to ubiquitin-dependent proteolysis of the following during anaphase

Cyclin B (required for exit from mitosis) and Securin (required for separation of sister chromatids); securin inhibits the protease separase which degrades cohesin, an SMC protein that holds sister chromatids together. Therefore, destruction of securin allows separase to digest cohesin and release sister chromatids.

Inventory of proteins required for cytokinesis

Cytokinesis of Drosophila and fission yeast depends on the same set of ~30 proteins, but the regulatory networks are not well understood

Metaphase spindle assembly checkpoint:

Delays separation of daughter chromatids until all are attached to the mitotic spindle.

Apoptosis differs from necrosis in that necrosis

During necrosis, cells swell causing the plasma membrane to burst and release the contents of the cell

Cancer metastasis requires an epithelial to meschymal transition

EMTs involve loss of cadherin mediated adhesion

totipotent

Embryonic cells within the first couple of cell divisions after fertilization are the only cells that are

The G2 checkpoint monitors for DNA damage or incomplete replication and delays the cell cycle in late G2 to provide time for DNA repair mechanisms to correct the problems.

Failure of this checkpoint allows cells with damaged DNA to attempt division, often leading to cell death.

Caspases

Family of cystein proteases that are activated at early stages of apoptosis and are responsible for degradation during cell death. They also cleave themselves to function

Nuclear Changes in Prometaphase

Following disassembly of nuclear lamins, the nuclear envelope with associated lamin B breaks up into vesicles or is included with fragments of endoplasmic reticulum. Lamin A and nuclear pore components disperse in the cytoplasm. Kinetochores form discrete structures capable of binding microtubule plus ends.

The phases of the cell cycle

G1, S, G2 Mitosis and cytokinesis

Telomere-dependent Senescence

Germ line and early embryonic cells have endogenous telomerase activity. Somatic cells with or without telomerase, telomeres shorten to about 4-7 kilobases whereupon they become senescent. Telomere shortening and senescence can be prevented by introducing telomerase. [ectopic telomerase] However telomerase does not prevent senescence induced by telomere-independent stimuli. Telomere-dependent senescence can be prevented or delayed by inactivating p53 and/or RB. However telomeres continue to shorten until cells reach crisis. Cells in crisis must activate a telomere stabilization mechanism in order to survive.

Some chromatin within a cell is normally associated with the nuclear lamina. Is this chromatin generally

Heterochromatin

A proposed model for the roles of IAPs and anti‐IAPs in the control of apoptosis in mammalian cells.

IAP's will block caspases if the procaspace cleaves

Inactive CAD is bound to

ICAD

Caspases break down

ICAD to set CAD free

Hemocyte

Immune cells that circulate within the hemolymph of insects and ingest foreign substances by phagocytosis; secrete antimicrobial peptides

Gastrulation

In animal development, a series of cell and tissue movements in which the blastula-stage embryo folds inward, producing a three-layered embryo, the gastrula.

Histone genes are activated during S phase to double the histone content of the cell by means of the following

Increasing transcription of the numerous histone genes. Increasing the rate of histone mRNA processing. Stabilizing histone mRNAs from degradation.

IAP stands for

Inhibitors of apoptosis

Metaphase

Interactions with microtubules align chromosomes in a plane between the poles; the "metaphase checkpoint" delays mitosis until all chromosomes are attached to the spindle.

The Sir-2 gene is a histone and other protein de-acetylase

It acts to silence genes at specific loci leading to increased life span. [Yeasts and nematodes] [Turns off aging genes] Sir-2 requires NAD+. Gene silencing can also be mediated by small [silencing] RNAs

Metaphase checkpoint:

Kinetochores lacking attached microtubules bind protein kinases (BubR1) that inhibit the transition to anaphase through a series of interactions: BubR1 phosphorylates Mad1p II, Mad1p activates Mad2p II, and Mad2p inhibits APC/C.

Tumor suppressor pRb

Loss of function mutations predisposes to eye tumors called retinoblastomas

Maturating Promoting Factor

MPF

Prophase in details with regard to the cytoplasm

Maturation of centrosomes: Polo kinase and aurora A kinase promote association of γ-tubulin ring complexes with the centrosome, resulting in more active nucleation of microtubules in mitosis than in interphase. Microtubules are more dynamic and shorter than in interphase owing largely to a reduction in the probability of rescue; this dynamic state allows them to search for kinetochores. Cdk1/cyclin B (and possibly other kinases) phosphorylate nuclear lamins, causing them to disassemble along with most other intermediate filaments. The Golgi apparatus disperses into vesicles: Budding continues while Cdk1/cyclin B phosphorylates and inhibits a protein required for fusion of transport vesicles back to the Golgi apparatus. Endoplasmic reticulum breaks up into vesicles. Cdk1/cyclin B phosphorylates elongation factor EF2a, which stops protein synthesis.

M

Mitosis and cytokinesis separate the replicated genome into two daughter cells.

G1 restriction point

Monitors cell size, environmental conditions, and interactions with neighbors and matrix

The role of survival factors and cell death in adjusting the nuber of developing nerve cells to the amount of target tissue

More nerve cells are produced nthan can be supported by the limited amount of survival factors released by the target cells. Therefore, some cells receive an insufficient amount of survival factors to avoid apoptosis. This strategy of overproduction followed by culling ensured that all target cells are contacted by nerve cells and that the extra nerve cells are automatically eliminated

Go

Most differentiated cells in higher eukaryotes withdraw from the cell cycle into this stage.

myc

Myc protein is a transcription factor that activates expression of many genes through binding on consensus sequences (Enhancer Box sequences (E-boxes)) and recruiting histone acetyltransferases (HATs). It can also act as a transcriptional repressor. By binding Miz-1 transcription factor and displacing the p300 co-activator, it inhibits expression of Miz-1 target genes. In addition, myc has a direct role in the control of DNA replication

Prometaphase

Nuclear envelope disassembles and microtubules growing from the poles seek and attach to kinetochores of condensed chromosomes

Telophase in detail

Once the chromosomes reach the poles, the nuclear envelope reassembles on their surfaces. Lamins are dephosphorylated; they bind chromatin and anchor nuclear envelope vesicles to the chromosomes. These vesicles fuse to form a continuous nuclear envelope. Nuclear pores reassemble and transport lamin A back into the nucleus for incorporation into lamin

Cyclin binding activates Cdks by altering the conformation of the active site; thus Cdk activity fluctuates across the cell cycle with the cellular cyclin levels.

Particular cyclins are synthesized and degraded for each cell cycle transition

How Bcl-‐2 proteins work

Puma tells cell to die

Contractile ring

Separation of daughter cells at the end of mitosis depends on the formation and constriction of an equatorial "______" composed of actin filaments, myosin-II, and associated proteins.

Anaphase

Severing of physical connections between sister chromatids allows them to separate and move toward the poles of the mitotic spindle (anaphase A). The poles of the spindle also move apart (anaphase B)

The Werner phenotype

Short stature, accelerated atherosclerosis, ateriosclerosis, graying of the hair, type II diabetes, cataracts, osteoporosis, and thymic atrophy.

replication origin

Site on a chromosome at which DNA replication begins. where initiator proteins aggregate

BH3 proteins differ in killing potential

Some killers have better attachment affinity

G1/S DNA damage checkpoint

Stops the cell cycle if DNA damage is detected

A combination of mitotic kinases triggers the onset of DNA replication. This involves the following

Synthesis of Cdks, proteins that fire the origins and replication proteins (such as DNA polymerase) as the cell passes the restriction point. Activation of Cdks by phosphorylation and dephosphorylation. Inactivation of Cdk inhibitor p27 by SCF

Apoptosis Depends on an Intracellular Proteolytic Cascade

That Is Mediated By Caspases

Cyclin B is a mitotic cyclin

The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-Cdk complex rise through the cell cycle[2] until mitosis, where they fall abruptly due to degradation of cyclin B (Cdk1 is constitutively present).[3] The complex of Cdk and cyclin B is called maturation promoting factor or mitosis promoting factor

Telophase

The chromatids complete their movements to the poles, and the nuclear envelope reforms around clusters of separated chromatids

Nuclear lamina structure and stem cell maintenance

The chromatins are in a more open state in stem cells

P27

The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. It is often referred to as a cell cycle inhibitor protein because its major function is to stop or slow down the cell division cycle.

missense mutations

The most common type of mutation, a base-pair substitution in which the new codon makes sense in that it still codes for an amino acid.

Hayflick and Moorhead's experiment to determine whether cells grown in culture have a finite life span

They apparently do.

Sirtuins [SIRT1-7] are a family of seven proteins linked to aging, metabolism and stress tolerance

They are considered anti-aging proteins. Increasing their activity retards aging. They catalyze either ATP-dependent deacetylation or ADP-ribosylation. Both mechanisms require the cleavage of NAD to form nicotinamide. SIRT1 regulates important aspects of mitochondria. During caloric restriction or by activation by certain small molecules, SIRT1 deacetylates PGC-ά which promotes biogenesis of mitochondria, improving mitochondrial function and decreasing the rate of ROS formation. Increased surface area of mitochondria lowers the hyper-polarization of the mitochondrial membrane that occurs when electrons get stalled along the electron transport chain which causes protons to be pumped to the cytoplasm leading to ROS.

Properties and functions of mammalian sirtuins

They have diversified in our own bodies as opposed to others

E2F

Transcription activator - when heterodimer with DP1 ---inhibitor when bound to Rb

Wnt signaling

Type of signaling that secretes a molecule that makes a cell express genes that it wouldn't otherwise do

Constriction of the contractile ring

Well after the contractile ring assembles around the equator, a still mysterious signal triggers its constriction. In some cells this involves transient release of Ca2+ around the equator and likely activation of myosin light-chain kinase, which turns on the contraction. The contractile ring disassembles as it constricts around the remnants of the central spindle. The central spindle condenses into a tightly packed overlapping array of microtubules called a mid-body, which occupies the intercellular bridge between the daughter cells

A proposed model for the roles of IAPs and anti‐IAPs in the control of apoptosis in mammalian cells. part 2

When cytochome c is release anti-iap is also released

How were essential components of the cell cycle discovered

Yeast models were used for genetic analysis of cell cycle control and the Sea urchin was used for biochemical analysis of cell cycle

SCF

a G1/S E3 ubiquitin ligase dependent on phosphorylation.

If genome replication is complete and the G2 checkpoint finds no DNA damage, then

a cascade of reactions triggers the transition from G2 into mitosis: Polo kinase activates Cdc25 phosphatase, which removes inhibitory phosphates from Cdk1. Active Cdk1/cyclin B also activates Cdc25 phosphatase, creating a positive feedback loop for Cdk1/cyclin B activation. Accumulation of active Cdk1/cyclin B in the nucleus pushes the cell into mitosis.

Telomeres form

a loop structure, the telosome/shelterin complex , containing a six protein complex. During DNA replication the presence of WRN enables the efficient replication of telomeric DNA by telomerase.

beta catenin

a protein that can act as an anchor for cadherins or as a transcription factor (induced by the Wnt pathway); important in the specification of germ layers.

philadelphia chromosome

a shortened chromosome produced when a large portion of chromosome 22 is exchanged with a small fragment from a tip of chromosome 9

CAK kinase

activates the cyclin-CDK complex by phosphorylating threonine residue 160 in the CDK activation loop. ___ itself is a member of the Cdk family and functions as a positive regulator of Cdk1, Cdk2, Cdk4, and Cdk6.[1]

The Hub keeps a cell a stem cell via

adhesion and signaling factors

TUNEL staining

allows the visualization of apoptotic. Where you label the ends of DNA

Cells that lack contact inhibitions

also compromises the structure of the tissue

The "incomplete replication checkpoint"

also involves ATM kinase, which activates Wee1, strengthening the inhibition of Cdk1/cyclin B and delaying entry into mitosis.

Procaspase

also known as zymogens where the prodomain gets cut off so a caspase can form

Humans have >10 Cdk

and 16 cyclin genes.

Red blood cells are constantly turning over

and have to be replaced by hematopoietic stem cells

An assembly of proteins called origin recognition complex (ORC) binds (yeast) origins throughout the cell cycle

and helps to organize a larger assembly called the prereplication complex that is required to "fire" the origin to begin DNA synthesis

Electron transport via NADH generates NAD+ in mitochondria a

and may decline with age

Cyclin-dependent kinases inhibit assembly of prereplication complexes

and therefore they assemble only once after mitosis when Cdk activity is low prior to passing the restriction point.

Somehow a cell can tell how big it is

and will divide when it is the right size

Stem cells

are cells defined by their ability to self renew and differentiate into mature cell types.

LIF and BMP

are important in keeping the pluripotentcy

Satellite cells

are muscle stem cells

Hematopoietic stem cells (HSCs)

are the blood cells that give rise to all the other blood cells and are derived from mesoderm. They are located in the red bone marrow, which is contained in the core of most bones.

RTK

are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins

Chromatin state changes

between stem and differentiated cell types

Epitote

binding site on the antigen

m-cyclin

binds to cdk before mitosis, triggering mitosis machinery

Senescent and Quiescent cells both

both exist in the G0/G1 phase of the cell cycle.

Active p53 can arrest the cell cycle in G1

by stimulating the expression of Cdk inhibitors or can induce cell death

If you over express ced-4 and ced-3

can kill a lot of cells

Old cells

can look different and can be so old that they get targeted by the immune system

accumulation of rDNA circles

can prevent a cell from dividing

Heritable epigenetics change

can silence a tumor suppressor

Sarcoma

cancer that begins in bone, cartilage, fat, muscle, blood vessels or other connective or supportive tissue.

Carcinoma

cancer that begins in the skin or in tissues that line or cover internal organs. There are a number of subtypes of carcinoma, inclyuding adenocarcinoma, basal cell carcinoma, sqamous cell carcinoma and transitional cell carcinoma

Leukenia

cancer that starts in blood forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood

lymphoma and myeloma

cancers that begin in the cells of the immune system

Central nervous system cancers

cancers that begin in the tissues of the brain and spinal cord

Transforming growth factor beta (TGF-β)

causes synthesis of p15 and p21 proteins, which block the cyclin:CDK complex responsible for Retinoblastoma protein (Rb) phosphorylation. Thus ___ blocks advance through the G1 phase of the cycle.[9] In doing so, ____ suppresses expression of c-myc, a gene which is involved in G1 cell cycle progression.

Interactions among egl-1, ced-9 ced-4 and ced-3 using genetic epistasis experiments

ced gene stands for cell death abnormal. egl means egg laying defective

CDC means

cell division cycle

During the blastocycst phase

cells are pluripotent but cannot give rise to the extra embryonic tissues

During early embryonic development

cells divide synchronously until a certain point

BH3 proteins monitor

cellular wellbeing

Sirtuins may be invoved with

chromosome repression

The G2 DNA damage checkpoint shares

components with the G1 DNA damage checkpoint and Two types of protein complexes sense DNA damage (by an unknown mechanism).

The great hallmark of cancer is that they lose

contact inhibition

Killer lymphocyte

contains the fas ligand which attaches to the death receptor

Mammalian target of rapamycin (mTOR)

controls protein synthesis.

Evidence for the genetic control of aging

daf2 codes for an insulin like growth factor. Both genes are involved in metabolism

Cell division rates

depend on the amount of nutrients present

Cdk4/cyclin D phosphorylates pRb,

dissociating the repressive complex, which allows for acetylation of local chromatin and expression of genes required for cell cycle progression in the G1 phase

prereplication complexes assemble

during the G1 phase

The ABL1 proto-oncogene

encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of ABL1 protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene.

Hypoxia Induces

epithelial to mesenchymal transition

Chemotherapy kills

fast growing cells

Life span decreases as

food intake increases. And Fecundity [reproductive capacity] increases as food intake increases.

ES and iPS Cells Are Useful

for Drug Discovery and Analysis of Disease

Mother and daughter centrioles remain linked (when)

from mitosis through G1 , S, and G2

Fgf pathway

further inhibits BMP

Telomeres protect chromosomes from fusion events

fusion occurs in a state of crisis

Stem cell niches

give stem cells the necessary environments to keep their "stemness"

PARP is involved

in DNA breaks

Caspases drive nuclear disassembly

in apoptosis. Nuclear lamins as well a Parp

Newly replicated DNA is packaged

in new nucleosomes

Conditional mutations allow the protein to function properly

in one condition but not in another (temperature is the condition for these experiments)These mutations are most often missense mutations that destabilize or disrupt protein interactions at the restrictive temperature (high temperature)

Wee1

inhibits Cdk1 by phosphorylating it on two different sites, Tyr15 and Thr14.[3] Cdk1 is crucial for the cyclin-dependent passage of the various cell cycle checkpoints. At least three checkpoints exist for which the inhibition of Cdk1 by Wee1 is important:

Catalase

is a common enzyme found in nearly all living organisms exposed to oxygen (such as vegetables, fruit or animals). It catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting the cell from oxidative damage by reactive oxygen species (ROS).

Poly (ADP-ribose) polymerase (PARP)

is a family of proteins involved in a number of cellular processes involving mainly DNA repair and programmed cell death.

Contact inhibition

is a growth mechanism which functions to keep cells growing into a layer one cell thick (a monolayer). If a cell has plenty of free space, it replicates rapidly and moves freely. This process keeps happening until the cells have divided so many times there is no longer any room in the layer for them to replicate. At this point, normal cells will stop replicating.

Mad2

is a key component of the spindle checkpoint, a device that controls the fidelity of chromosome segregation in mitosis

ORC or origin recognition complex

is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes in an ATP-dependent manner to origins of replication.

Securin

is a protein involved in control of the metaphase-anaphase transition and anaphase onset. Following bi-orientation of chromosome pairs and inactivation of the spindle checkpoint system, the underlying regulatory system, which includes ___, produces an abrupt stimulus that induces highly synchronous chromosome separation

licensing factor

is a protein or complex of proteins that allows an origin of replication to begin DNA replication at that site. They are thought to primarily occur in eukaryotic cells, since prokaryotes use simpler systems to initiate replication

Anaphase-Promoting Complex (also called the cyclosome or APC/C)

is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11-13 subunit proteins, including a cullin (Apc2) and RING (Apc11) subunit much like SCF. Other parts of the APC/C still have unknown functions, but are highly conserved.[

Werner's Syndrome[WS]

is caused by a variety of loss-of-function mutations in a gene coding for a member of the RecQ helicase family[WRN]. WRN helicase interacts with a wide variety of proteins suggesting roles in DNA replication,recombination and apoptosis. Its main function blocks re-initiation of DNA replication at stalled replication forks. This triggers sensitivity to DNA damaging agents and a frequency of deletion mutations. The result is a very limited ability for cells to divide. In cell culture WRN fibroblasts can double about 20 times while normal fibroblasts can double 40 to 100 times. WS cells can be induced to re-initiate DNA replication by the insertion of a telomerase gene. BUT Why would this mutation result in the Werner Syndrome phenotype?

Mad1

is crucial for the localization of Mad2 to kinetochores, where Mad2 interacts with Cdc20

LAD

is lamina associated domains

Membrane fusion machinery

is required to complete the division of the cells.

The key defining aspect of a stem cell

is that it is undifferentiated and can continuously divide.

G1 phase, or Growth 1/Gap 1 phase

is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell grows in size and synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. G1 phase ends when the cell moves into the S phase of interphase

BMP

is used in inter digit formation

The partner cell of the stem cell

is usually differentiated

Explain how the ames test functions

it is explained

Cytochrome C has two lives

it is used in aerobic respiration and in apoptosis

Bubr1

kinase involved in spindle checkpoint function. The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation.

Viral genome intergration

leads to cancer

CAD protein

look up

INK

look up

mTOR

look up

In metaphase Kinetochore microtubules

maintain a constant length but treadmill slowly by addition of tubulin dimers at the kinetochores balanced by loss at the poles.

Besides cyclins, many other proteins regulate Cdk activity

many regulatory proteins regulated by protein degradation

The hippo pathway

mediates contact inhibition

Aysymmetric division

moving one cell from a signaling source

Biochemical experiments on protein synthesis in early embryos revealed proteins

named cyclins that are synthesized and destroyed in synchrony with cell cycle stages.

Synthesis of RNA and proteins occurs continuously during cell cycle, DNA synthesis only

occurs during S-phase

The phildelphia Chromosome causes an active form

of Abl to be produced

MPF turns out to consist

of a cyclin and a cdk

Apoptosis is promoted by the release

of cytochrome c into the cytosol from mitochondria.

Defects in a nuclear lamin can cause a rare class

of premature aging disorders called progeria

ABl kinase exists downstream

of the kit pathway

There are two types of apoptosis

one being intrinsic and the other extrinsic

G2

originally described as a gap between DNA replication and mitosis; now appreciated to be the time when cells check for completion of DNA replication before entering mitosis.

G1

originally described as a gap between mitosis and DNA replication; now appreciated to be the time when cells grow and check for DNA damage and sample the environment to make the pivotal decision to replicate their genomes and progress through the cell cycle.

Defects in the genes for ATM or p53

predispose to cancer, most likely from defects in the G1 checkpoint rather than from the G2 checkpoint

PCD means

programmed cell death which includes apoptosis and necrosis

Sea urchin was instrumental in the discovery of

proteins regulating the cell-cycle

The mt is always producing

reactive oxygen species which damages the cell

Stem cell niche

refers to a microenvironment where stem cells are found, which interacts with stem cells to regulate cell fate. This word can be in reference to the in vivo or in vitro stem cell microenvironment

Phosphorylation of a tyrosine and a threonine inhibits activity

removal by the Cdc25 tyrosine phosphatase promotes activity

Cells have biochemical mechanisms to repair damaged DNA, including

replacement of damaged or mismatched bases and even double-strand breaks.

SMC proteins (Structural Maintenance of Chromosomes)

represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics.

KIT pathway

signaling is plays important role in a number of physiological processes including erythropoiesis, lymphopoiesis, mast cell development and function, megakaryopoiesis, gametogenesis and melanogenesis.

The three types of stem cell niches are

simple niches, complex niches and storage niches

Some of the factors required to assemble the prereplication complex may only interact with chromosomes during mitosis,

since they are excluded from interphase nuclei by the nuclear pores. Thus, these "licensing factors" can act only once per cell cycle.

In the absence of growth stimuli, the complex of E2F/DP1, pRb, and histone deacetylase

targets and represses genes required for cell cycle progression by chromatin compaction in the G1 checkpoint

Werner's Syndrome [WS] is a premature aging syndrome

that is caused by a single gene mutation of WRN. The mutation results in a rapid onset of cellular senescence.

Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase

that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis. Several of these targets, including p53, CHK2 and H2AX are tumor suppressors.

Cdks (Cdk2/cyclin E or cyclin A) regulate

the centrosome replication, but the phosphorylated targets are not known.

Cells exit from mitosis when APC/C degrades

the cyclins required for mitotic Cdk activity.

Bcl2 Proteins Regulate

the intrinsic pathway of apoptosis and These proteins lead to the realease of cytochrome c

Epistasis experiments can determine

the order in which these genes function during the cell cycle

High-energy electrons are transferred between

three repiratory enzyme complexes

Phosphorylation of an activation loop (called the "T-loop")

threonine stimulates activity and phosphorylation of another threonine promotes binding to cyclins

A cell needs multiple mutations

to become cancer

Fadd adapaptor aggregates

to form the Disc complex which is similar to the apoptosome

Reactive oxygen species can lead

to the cellular accumulation of damaged biomolecules at all levels of cellular organization

You started as a

totipotent cell

E2f is a

transcription factor

FOXO

transcription factors that activate transcription of genes that inhibit cell proliferation & induce cell death

Cells evolved from

unicellular to clonal than multicellulcar

Modulatuion of inter-digit cell death has been

utilized during evolutionary adaption. Tgf beta signalling pathway is involed in apoptosis. The gremlin pathway can inhibit the bmp pathway. Fgf further eliminates cell death

You can detect oncogenes

via transfection

In transient amplifying population

when hemo stem cells go from slow dividing to fast dividing

Cells in G0 can re-enter the cell cycle

when stimulated by growth factors

S phase

when the genome is replicated

New daughter centrioles elongate until they reach full size early in mitosis

when the two mature centrosomes separate to form the poles of the mitotic spindle.

Combination therapies may succeed

where treatments with one drug at a time fail

ATM kinase phosphorylates Chk1 (checkpoint kinase 1),

which activates Chk1 to phosphorylate an inhibitory site on Cdc25, preventing activation of Cdk1/cyclin B and entry into mitosis

ATM kinase phosphorylates p53

which activates p53 to promote expression of Cdk inhibitors, leading to arrest of the cell cycle

During S phase new daughter centrioles form orthogonal to the existing centrioles,

which are then called the old mother centriole and new mother centriole.

In preparation for mitosis, cells synthesize cyclin B,

which associates with Cdk1 (the animal homologue of the famous fission yeast kinase Cdc2) present throughout the cell cycle but not active until the transition into M phase

Cells with one functional copy of a tumor suppressor gene

will usually proliferate faster than normal cells.

Life span increases

with education

Explain how cancer cells become more heterogeneous as they progress

with more mutations cancer cells can be different from each other

How to find tumors via Pet Scan

you administer to the patient radioactive glucose to see where the glucose will aggregate in the body

If you increase the activity of Sir2

you can increase the life span

Via apoptosis in early development

you can tell the exact amount of cells that die

If you increase catalase

you increase the life span of an animal because you can deal with the radical damage