Exam 3

Programmed cell death occurs ________________. A. by means of an intracellular suicide program. B. rarely and selectively only during animal development. C. only in unhealthy or abnormal cells. D. only during embryonic development.

A

Which of the following statements regarding Fas-mediated programmed cell death is false? A. Fas ligand binding with Fas receptor stimulates a specific G protein. B. Fas ligand and receptor interaction results in the recruitment of adaptor proteins in the target cell. C. Capases are activated in the process. D. The caspase cascade results in the cleavage of the proteins within the target cell. E. It ultimately results in death of the cell.

A

By what mechanism are receptor tyrosine kinases (RTKs) activated?

A ligand binds to the RTK receptor, and causes two of them to cluster together. This clustering (close association) activates their catalytic cytoplasmic domains. Once activated, the two domains phosphorylate each other on tyrosine residues through a process called autophosphorylation. The phosphorylated cytoplasmic tails then interact with proteins inside the cell that promotes a signaling cascade (signal transduction pathway).

Which are required for the formation and function of the mitotic spindle? Choose all that apply. A. Microtubules B. Centrosome C. Kinetochore D. Actin E. Motor proteins

A, B, C, E

In what ways are CDKs regulated? (choose all that apply) A. by cyclins B. by inhibitors C. transcriptionally D. through targeted degradation E. by phosphorylating/dephosphorylating CDKs

A, B, E

Which of the following genetic changes cannot convert a proto-oncogene into an oncogene? A. A mutation that introduces a stop codon immediately after the codon for the initiator methionine. B. A mutation within the coding sequence that makes the protein hyperactive. C. An amplification of the number of copies of the proto-oncogene, causing overproduction of the normal protein. D. A mutation in the promoter of the proto-oncogene, causing the normal protein to be transcribed and translated at an abnormally high level. E. A mutation that introduces a stop codon immediately after the codon for the initiator methionine will result in no protein being produced. Proto-oncogenes become oncogenes when they acquire mutations that cause them to act in a dominant hyperactive manner

A, E

What is the mechanism of the spindle checkpoint... c) What is the function/purpose of the anaphase-promoting complex when the spindle checkpoint is off?

APC degrades the protein securin. Once securin is degraded, separase is free to degrade cohesins which help hold sister chromatids together. It also degrades the mitotic cyclin-CDK complex (MPF), which allows exit from mitosis (cytokinesis happens, chromosomes decondense, nuclear envelope reforms, etc).

Explain the concept of genetic instability.

Accumulation of genetic and epigenetic changes which further perpetuate more mutations. This also includes cases in which chromosome are inappropriately fused together (possibly because of telomere loss) and then subsequently broken during mitosis.

How is anaphase A different than anaphase B?

Anaphase A is the chromosomes (once sister chromatids) moving toward the poles of the cell; anaphase B the separation of the poles of the cell.

What happens at the M checkpoint (aka the spindle checkpoint) in the cell cycle?

At the M check point, the cell checks whether each chromatid is attached to the mitotic spindle at its kinetochore. This ensures that the chromatids can be pulled to opposite poles in anaphase and that the resulting cells will have an equal number of chromosomes. If some of the kinetochores are not attached to the spindle, anaphase does not start.

Killer lymphocytes can elicit self-destruct mechanisms in target cells by interacting with A. Fas ligand. B. Fas receptors. C. Ras ligand. D. adaptor proteins. E. procaspase.

B

Which of the following statements about tumor suppressor genes is false? A. Gene amplification of a tumor suppressor gene is less dangerous than gene amplification of a proto-oncogene. B. Cells with one functional copy of a tumor suppressor gene will usually proliferate faster than normal cells. C. Inactivation of tumor suppressor genes leads to enhanced cell survival and proliferation. D. Individuals with only one functional copy of a tumor suppressor gene are more prone to cancer than individuals with two functional copies of a tumor suppressor gene.

B

Which of the following alterations could directly cause a cell to proliferate more than it should? Choose all that apply. A. Loss of a protein that normally inhibits apoptosis B. Loss of a protein that normally promotes apoptosis C. Loss of a protein that normally prevents progress through the cell cycle if there is something wrong D. Mutation of a protein that corrects DNA damage

B, C

In what ways are cyclins regulated? (choose all that apply) A. by inhibitors B. transcriptionally C. through mitogens (e.g., growth factors) D. through targeted degradation E. by phosphorylating/dephosphorylating CDKs

B, C, D

What would be the effect in an organism that had a mutated version of the Bcl-2 protein?

Bcl-2 normally inhibits apoptosis and promotes cell survival. If Bcl-2 were mutated, it would likely lose its normal function, and wouldn't promote cell survival, likely leading to apoptosis.

Apoptosis differs from necrosis in that necrosis ________________. A. requires the reception of an extracellular signal. B. causes DNA to fragment. C. causes cells to swell and burst, whereas apoptotic cells shrink and condense. D. involves a caspase cascade.

C

Predict what happens when there is a mutation that inactivates the kinase part of cyclin-dependent kinase.

CDK won't be able to phosphorylate its targets so cyclin-CDK complex won't be active. Cell cycle stops at that point and would slow down cell division.

How do cancer cells become metastatic?

Cancer cells secrete proteins that promote angiogenesis, thereby providing a blood supply for the growing tumor. They also secrete proteins that degrade extracellular matrix, which aids in their ability to migrate into surrounding tissues and aids in blood vessel cells to migrate toward the tumor. In the case of epithelial cancers, the cells break through the basal lamina that divides the epithelial layer from the underlying tissue. The cells migrate through the tissue and enter the blood stream that way. Part of the reason all of this is possible is because cancer cells will experience an epithelial to mesenchymal transition in which the cells lose their polarity and lose their adhesive characteristics. Thus, they're able to migrate and invade surrounding tissues and the blood stream.

For each of the following, state specifically how the treatment would be expected to stimulate or inhibit apoptosis. Treatment of cells with organic compounds that enter the cell and bind with high affinity to the active site of caspase-3.

Caspase-3 is a key activator of the apoptosis pathway, so inhibiting it would suppress cell death.

What are caspases? Explain the two basic kinds of caspases and how they're activated.

Caspases are proteases. They are enzymes that can degrade a huge variety of other proteins, and are necessary to break down the cellular components during apoptosis and to activate other caspases. The two kinds of caspases are initiator caspases and executioner caspases. Both varieties start out as inactive procaspases. Initiator caspases are activated by other caspases (I don't know how the original one gets activated...) through cleavage at certain sites that allows the initiator caspases to dimerize. The initiator caspases then go on to activate executioner caspases by a similar mechanism. The executioner caspases can either go on to active more executioner caspases, or start degrading cellular proteins such as nuclear lamin or cytosolic proteins.

What are ways in which a proto-oncogene can be converted to an oncogene?

Causing the protein to be hyperactive, meaning it is resistant to being "turned off" or even degradation; when the gene is duplicated such that more protein product is made than there should be for normal regulation; chromosome rearrangements in which the coding region of the gene is placed downstream of a promoter that is turned on all the time (or a lot of the time).

Of what are centrosomes composed and what is their purpose with respect to cell division?

Centrosomes are composed of centrioles and pericentriolar material. Centrosomes are the structures from which microtubules are derived. The minus end of MTs is anchored at the centrosome/pericentriolar material.

What is the mechanism of the spindle checkpoint... a) When all chromosomes are attached to spindles? Is the checkpoint on or off?

Checkpoint is off. Anaphase promoting complex (APC) is activated (it is bound by Cdc20), which allows the initiation of anaphase

What is the mechanism of the spindle checkpoint... b) In the presence of unattached spindles? Is the checkpoint on or off?

Checkpoint is on. Cdc20 is bound to proteins at the kinetochore, therefore not allowing it to bind to APC. Since it's not bound to APC, anaphase is not initiated.

A malignant tumor is more dangerous than a benign tumor because ______________________. A. its cells are proliferating faster. B. it causes neighboring cells to mutate. C. its cells attack and phagocytose neighboring normal tissue cells. D. its cells invade other tissues.

D

All of the following can participate in apoptosis except A. caspases. B. death-promoting proteins. C. mitochondria. D. Bcl-2. E. cytochrome c.

D

Which trigger stops a cell prior to allowing anaphase to occur? A. An intact nuclear envelope. B. A cell floating in suspension. C. Incomplete non-kinetochore microtubules. D. A kinetochore not attached to a microtubule.

D

What is the original cause of all cancers?

DNA mutations in genes (proto-oncogenes or tumor-suppressor genes) or important regulatory regions.

What is happening in the S phase of the cell cycle?

DNA replication/ duplication of cellular components

When an animal cell is treated with colchicine, a chemical that binds -tubulin, its MTs depolymerize and virtually disappear. If the colchicine is then washed away, the MTs appear again, beginning at the centrosome and elongating outward. Explain this result.

If beta-tubulin is inhibited, then microtubule polymerization will also be inhibited. Once the drug is diluted out (washed away), beta-tubulin is free to bind to alpha-tubulin, and the dimer can then be added to the "plus" end of a microtubule (starting at gamma-tubulin at the base) for polymerization

Explain why p53 is referred to as "the guardian of the genome".

It is responsible for helping control the DNA damage (G1) checkpoint. If DNA damage occurs, p53 becomes phosphorylated, stabilized and activated. It stimulates signal transduction pathways that will temporarily stop the cell cycle to allow the DNA damage to be repaired. In cases where there is too much DNA damage and it can't be repaired, p53 will promote a different pathway that leads to the cell committing suicide (apoptosis). It also activates transcription of genes that help repair the damaged DNA.

Why is interphase so long while mitosis/cytokinesis is so short?

It takes time to grow, make more macromolecules, replicate DNA, make more organelles, etc, all of which takes place during interphase. Splitting of everything (DNA, organelles, etc) is a much faster process.

What would be the effect in an organism that harbored a version of the 'Bad' protein that couldn't be phosphorylated (aka a bad Bad protein)?

It wouldn't be able to release its inhibitory effects on Bcl-2, keeping it inactive. Cell survival wouldn't be promoted; rather apoptosis was be more likely.

Explain the relationship between centromeres and kinetochores.

Kinetochores are proteinaceous structures that associate with the centromeres. During mitosis, it is the kinetochore that MTs are actually binding to. Inner kinetochore proteins interact with centromeric DNA and outer kinetochore proteins. Outer kinetochore proteins directly interact with the MTs

What are apoptosomes?

Large multimeric proteins that aid in the process of apoptosis

What is the role of the mitochondria and cytochrome c in apoptosis?

Mitochondria is part of the intrinsic apoptotic pathway. Once the appropriate signal is received, cytochrome c is released which kind of initiates the formation of apoptosomes

Why is it so bad when a cancer becomes metastatic?

Once cancer cells are in the blood stream, they can exit the blood stream at any point and invade a secondary site, spreading the cancer throughout the body.

Indicate whether each of the following descriptions applies to an oncogene, a proto-oncogene, or a tumor suppressor gene. Some descriptions may apply to more than one of these gene types. e. A gene whose presence can cause cancer

Oncogenes are genes whose presence can cause cancer.

Indicate whether each of the following descriptions applies to an oncogene, a proto-oncogene, or a tumor suppressor gene. Some descriptions may apply to more than one of these gene types. c. A type of gene found in cancer cells

Oncogenes can be found in cancer cells. However, cancer cells also contain many normal proto-oncogenes and tumor suppressor genes. Only a small number of the dozens of proto-oncogenes and tumor suppressor genes in a normal cell need to be mutated to trigger the development of cancer.

Describe the basic mechanism of how the creation of a skin wound causes a signaling cascade.

PDGF is released from the blood and signals to nearby fibroblasts within the tissue. The PDGF ligand binds to its receptor (PDGF receptor) on the cell surface. The signal is communicated to the inside of the cell through a signaling cascade that involves several enzymes/proteins. The signal is amplified and reaches a target, which causes the fibroblasts to divide (get past the G1 checkpoint of the cell cycle) and migrate.

How is the nuclear envelope broken down during cell division? When is it broken down?

Pore proteins and nuclear envelope components (including nuclear lamins) are phosphorylated (by MPF) . This causes them to dissociate from one another, effectively breaking down the nuclear envelope. It's broken down during prometaphase.

The number of cells in an adult tissue or animal depends on cell proliferation. What else does it depend on?

Programmed cell death also influences cell numbers. Most animal cells require survival signals from other cells to avoid programmed cell death, so that the levels of such signals can help determine how many cells live and how many die.

Indicate whether each of the following descriptions applies to an oncogene, a proto-oncogene, or a tumor suppressor gene. Some descriptions may apply to more than one of these gene types. a. A type of gene found in normal cells

Proto-oncogenes and tumor suppressor genes are both found in normal cells. Oncogenes are genes whose presence causes cancer and so are not typically found in normal cells.

Indicate whether each of the following descriptions applies to an oncogene, a proto-oncogene, or a tumor suppressor gene. Some descriptions may apply to more than one of these gene types. b. A gene that could encode a normal growth factor

Proto-oncogenes encode normal growth factors. Although oncogenes often encode abnormal versions of proto-oncogene proteins, they can also encode excessive quantities of a normal protein encoded by a proto-oncogene. Hence, an oncogene could result from excessive amounts of a normal growth factor.

What are some characteristics of proto-oncogenes? Of tumor-suppressor genes?

Proto-oncogenes: normal function is to promote cell growth. When mutated, often cause gain-of-function mutations, which are dominant, and thereby convert them into oncogenes. Only one mutant allele is necessary to cause the cancerous phenotype of excessive cell survival and proliferation. Tumor-suppressors: normal function is to prevent cell growth. When mutated, often cause loss-of-function mutation, which are recessive. Therefore, two mutant alleles are required to eliminate all function and cause the cancerous phenotype of excessive cell survival and proliferation.

What would happen if there was a mutation in one of the components of the anaphase promoting complex (APC)?

Securin wouldn't be degraded, meaning sister chromatids wouldn't separate. Also, mitotic CDK-cyclin wouldn't be degraded, meaning the cell wouldn't be able to exit mitosis—nuclear envelope wouldn't reform, chromosomes wouldn't decondense (transcription and translation couldn't occur), etc. The cell wouldn't be in good shape

State specifically how the treatment would be expected to stimulate or inhibit apoptosis. Cells are treated with a small molecule called pifithrin-alpha, which was originally isolated for its ability to reversibly block p53-dependent transcriptional activation.

Since pifithrin-alpha reversibly blocks p53-dependent transcriptional activation, one might expect two effects: (1) p21 would not be expressed, leading to loss of cell cycle arrest (i.e., continuation of the cell cycle), and (2) Puma would not be expressed, leading to less efficient inhibition of mitosis. In such cells, apoptosis would be less likely to occur, and they would be more likely to divide.

What is the cause of the massive amount of programmed cell death of nerve cells (neurons) that occurs in the developing vertebrate nervous system, and what purpose does it serve?

Immature neurons are produced in excess of the number that will eventually be required. They compete for the limited amount of survival factors secreted by the target cells they contact. Those cells that fail to get enough survival factors undergo programmed cell death. Up to half or more of the original nerve cells die in this way. This competitive mechanism helps match the number of developing nerve cells to the number of target cells they contact.

Indicate whether each of the following descriptions applies to an oncogene, a proto-oncogene, or a tumor suppressor gene. Some descriptions may apply to more than one of these gene types. d. A type of gene found only in cancer cells

In those cases when they arise from gene rearrangement or other mutations not found in a normal proto-oncogene, oncogenes are genes that are uniquely present in cancer cells.

What are intermediate filaments? Why are they relevant to cell division?

Intermediate filaments (IFs) are rope-like proteins and are a component of the cytoskeleton. They are relevant to cell division because the nuclear envelope, which is broken down and reformed during mitosis, is associated with a meshwork of IFs (i.e., the nuclear lamina).

What determines how a cancer is categorized?

It depends on the cell type from which it was derived. For example, all carcinomas are derived from an epithelial cell type whereas sarcomas are derived from cells of connective tissue (fibroblasts, bone, etc).

How is the extrinsic apoptotic pathway different from the intrinsic apoptotic pathway? How are they similar?

Extrinsic pathway relies on a signal from another cell. A ligand (e.g., Fas or TNF—tumor necrosis factor) from a "killer" cell binds to its receptor (the death receptor) on the target cell and initiates an intracellular suicide cascade. Mitochondria can be involved but isn't necessarily The intrinsic pathway starts from within the cell, from things like excessive DNA damage, ER stress due to misfolded proteins, absence of growth factors, etc). All of these internal signals converge on the mitochondria, which initiates the suicide cascade. Similar in that they both activate a series of caspases to promote cellular suicide

True or False: The energy required for tubulin polymerization is provided by hydrolysis of a nucleoside triphosphate. Explain.

False, hydrolysis of GTP (for MTs) is not required for polymerization of the molecules. Association with the molecules is required for stability of the interaction and thereby promotes polymerization.

You are studying cells that normally respond to epidermal growth factor (EGF) by increasing their rate of cell division. You measure the cell division rate in normal cells and in cells in which a GTPase activating protein (GAP—a protein that hydrolyzes GTP and inactivates Ras) has been mutated so that it no longer functions properly. When the two types of cells are exposed to the same concentration of EGF, what differences in response to EGF do you expect? Explain your answer.

GAPs (GTPase activating proteins) cause the more rapid inactivation of Ras because they stimulate Ras to hydrolyze its associated GTP to GDP. When the GAP is missing, Ras will remain active for a longer period of time, leading to an increase in cell division compared with untreated control cells.

The amount of dynamic instability exhibited by microtubules varies depending on the kind of cell and whether it is dividing. Under what circumstances might you expect dynamic instability to be greatest, and why?

Greater dynamic instability leads to more rapid shrinkage and regrowth of MTs. This might be expected in situations where the cell is undergoing rapid, dynamic changes. One example is mitosis, when a dividing cell must construct or destruct the spindle.

What is happening in the M phase of the cell cycle?

mitosis

Which would you expect to be more sensitive to treatment with radiation—tumors with wild-type p53 genes or tumors with mutated p53 genes?

p53 is required for cell cycle arrest and apoptosis in response to DNA damage induced by ionizing radiation. Thus, tumors with wild-type p53 genes will be more sensitive to radiation.

Why are mutations in p53 so detrimental to the cell and found in so many cancers?

p53 is the "guardian of the genome". When there is DNA damage it becomes phosphorylated and stabilized, allowing it to halt the cell cycle to allow time for repair, or in the case that the DNA damage is too great, it can promote the apoptosis pathway. When it's mutated, it can no longer help with the DNA repair response, which causes an accumulation of mutations. It can also no longer promote apoptosis, which allows these cells with multiple mutations to continue to survive and proliferate.

What components make up apoptosomes?

cytochrome c release from the mitochondrial matrix interacts with an adaptor protein to make a heptameric circular structure. Procaspase-9 joins at multiple places in the heptamer and becomes activated.

What is happening in the cytokinesis phase of the cell cycle?

division of cytoplasmic contents, separation of 1 plasma membrane into 2

What is happening in the G2 phase of the cell cycle?

growth/ duplication of cellular components (see list from G1; also included is centrosomes)

What is happening in the G1 phase of the cell cycle?

growth/ duplication of cellular components (things like cytoplasm, protein, ribosomes, carbohydrates, ER, Golgi, etc.)

What is metastasis?

ability of cancer cells to enter the blood stream

Why do cyclin and MPF (mitosis promoting factor) peak at the same time but rise at different rates?

They peak at the same time because cyclin is part of MPF; it binds to Cdk, forming MPF. They rise at different rates because cyclin is produced throughout S phase and G2 phase, but MPF is only formed (and active) when cyclin binds to Cdk.

Progeria is a disease that is associated with early, rapid aging and is due to a mutation in a gene that encodes one of the intermediate filaments. The mutation causes defects in post-translational modifications. Speculate what is happening at the cellular level to cause the disease.

Since the protein is farnesylated, it is localized to the nucleus properly, but the deletion of 50 amino acids prevents normal cleavage of the C-terminal end containing the farnesyl. This prevents properly assembly of intermediate filaments to make up the nuclear lamina, leading to an unstable nucleus. The nuclear lamina contributes to proper organization of the genetic material (telomeres, centromeres, maintenance of epigenetic marks, etc) in the nucleus as well as processes such as replication and transcription. The instability of the nuclear lamina, the nucleus itself and the genome leads to a variety of effects associated with aging.

In the case of DNA damage, how is the cell cycle altered? Comment on the role of p53, Cdk inhibitors, and activity of CDK-cyclin.

Surveillance proteins recognize the DNA damage and elicit a response that leads to phosphorylation of p53, stabilizing it. This causes p21 to inhibit the activity of CDK-cyclin. Since the CDK-cyclin complex is not activated, Rb can't be phosphorylated and the genes products required for S phase will not be expressed. Thus, the cell cycle will not proceed until the DNA damage is repaired.

State specifically how the treatment would be expected to stimulate or inhibit apoptosis. Exposing cells to recombinant TRAIL protein, a ligand for the tumor necrosis factor family of receptors (i.e., death receptors).

TRAIL would activate pathways similar to TNF-alpha, a known stimulator of apoptosis.

How does a Cyclin-Cdk complex form, and how is it activated?

The complex is made of two subunits: the kinase subunit and the cyclin subunit. The complex forms once a critical concentration of cyclin is reached. It is activated when the cyclin and kinase subunits form a complex (bind/interact with each other) and the kinase subunit is dephosphorylated (shown later in the power point).

If there is a mutation in a cyclin that makes the protein present all the time, what affect would that have on the cell cycle? Explain your answer.

The cyclin-CDK complex would always be active. It would cause the cell to want to push through that particular phase of the cell cycle more frequently, causing the cell to probably divide more often than it should. Leads to unregulated cell division (cancer!).

A certain mutation in the receptor for epidermal growth factor (EGF) causes the mutated receptor protein to send a positive signal along the associated intracellular signaling pathway even when the EGF ligand is not bound to it. This signal leads to abnormal cell proliferation in the absence of growth factor. On the basis of this information, would you class the gene for the EGF receptor as a tumor suppressor gene or a potential oncogene? Explain your answer.

The mutation described leads toward cancerous cell behavior (excessive proliferation) by making the gene product hyperactive. The mutant gene is therefore, by definition, an oncogene. This effect is seen even if only one copy of the gene is affected; in other words, the mutation is dominant, as is typical for an oncogene. Mutations that delete an EGF receptor gene would be expected to have either no effect or an inhibiting effect on cell division. Thus, the normal EGF receptor is classed as a potential oncogene (a proto-oncogene).

Imagine that you could microinject cytochrome c into the cytosol of both wild-type cells and cells that were lacking both Bax and Bak, which are apoptosis-promoting members of the Bcl2 family of proteins. Would you expect one, both, or neither of the cell lines to undergo apoptosis? Explain your reasoning.

The presence or absence of Bak and Bax would not affect whether a microinjection of cytochrome c would promote apoptosis, because Bax and Bak act upstream of cytochrome c by promoting its release from mitochondria. By promoting the formation of the apoptosome and the activation of procaspases, microinjection of cytochrome c bypasses the need for Bax or Bak in promoting apoptosis.

Newborn mice deficient in Apaf1 or caspase-9 have distinctive abnormalities in their paws. Apaf1-deficient mice fail to eliminate the webs between their developing digits, whereas caspase-9-deficient mice have normally formed digits (see Figure to the right). If Apaf1 and caspase-9 function in the same apoptotic pathway, how is it possible for these deficient mice to differ in web-cell apoptosis?

The retention of the web cells in Apaf1-/- mice indicates that Apaf1 is essential for web-cell apoptosis, presumably in conjunction with cytochrome c. The absence of web cells in Casp9-/- mice indicates that caspase-9 is not required for web-cell apoptosis. These observations suggest that Apaf1 may activate a different caspase in web cells, instead of caspase-913.

What is the ultimate purpose of apoptosomes?

Their purpose is to activate a caspase cascade that leads to apoptosis

You are given two test tubes, one containing cells from a human cancer and the other containing normal cells. Before you begin your studies, the labels fall off the tubes. Describe how you could determine which sample contains the cancer cells.

There are multiple ways. You could inject some of the cells into an animal and see which causes tumor growth. You could culture them on plastic and see which culture doesn't have density-dependent or contact-dependent inhibition. A third way would be to maintain a population in cells for a longer period of time; the cells that are normal should only be able to divide about 50-60 times before senescence whereas the cancer cells will keep chugging along indefinitely.

How does microtubule growth occur?

There are proteins that somehow anchor to the pericentriolar material, one of which is gamma tubulin. This acts as the nucleation center for addition of the alpha and beta tubulin heterodimers to the plus end of the MT.

There is a protein called p16 that is an inhibitor of cyclin-dependent kinases (Cdks). If the cell produces more than normal amounts of p16, what effect will that have on the cell cycle. Explain your answer.

Too much inhibition of the CDK would also inhibit the cyclin/CDK complex activity, meaning the cell cycle will probably stop and cause no cell division

Indicate whether each of the following descriptions applies to an oncogene, a proto-oncogene, or a tumor suppressor gene. Some descriptions may apply to more than one of these gene types. g. A type of gene found in normal cells and cancer cells.

Tumor suppressor genes and proto-oncogenes are present in both normal cells and cancer cells. Their presence is explained by the fact that only a small number of the dozens of proto-oncogenes and tumor suppressor genes present in a normal cell need to be mutated to trigger the development of cancer.

Indicate whether each of the following descriptions applies to an oncogene, a proto-oncogene, or a tumor suppressor gene. Some descriptions may apply to more than one of these gene types. f. A gene whose absence can cause cancer

Tumor suppressor genes are genes whose absence can cause cancer.

How do cells get past the G1 restriction point? (A complete response will be pretty long.)

Usually through the external signals of growth factors like PDGF (platelet derived growth factor) or EGF (epidermal growth factor), for example. The growth factor binds its RTK receptor, the receptors cluster and autophosphorylate. Activated RTKs activate Ras by causing it to exchange its GDP for GTP. Ras-GTP starts a phosphorylation cascade in which a series of kinases become activated and then phosphorylate a substrate. Eventually, one of the kinases gets into the nucleus and activates transcription of genes required for the cycle to proceed past G1 (e.g., cyclins). Once cyclin reaches its critical concentration, it binds to CDK, and they become an active complex. Cyclin/CDK phosphorylates the Rb protein, causing it to change its conformation and release its inhibition of E2F transcription factor. This transcription factor becomes free to transcribe genes whose protein products are required for S phase (e.g., DNA polymerase, helicase, etc).