Cell Cycle, Apoptosis, and Cancer Flashcards
When is the restriction point (R), and what happens there?
2 hours prior to S phase (in G1)
if growth factors are limiting –> restriction occurs
What two proteins in HPV cause cancer?
E6 and E7
What happens in the G0 phase?
poor nutrient/environmental conditions –> cell withdraws from cell cycle
What do proto-oncogenes normally code for?
growth factors
receptors for GFs and hormones
Transcription factors
(basically anything promoting cell growth and division)
What is p53
transcription factor that is activated when DNA is damaged –> activates p21 –> keeps Rb hypophosphorylated and sequesters E2F so you can’t move into S phase
Promotes apoptosis = tumor suppressor
What does CDC25 phosphatase do?
Undoes WEE1 phosphorylation of C-CDK complex to reactivate it
When do topoisomerase I inhibitors work?
S, G2, and M phases
What does E6 in HPV inhibit?
p53
What are the checkpoints?
R, G1, G2, Metaphase
What is APC/C?
anaphase promoting complex/ cyclosome
a ubiquitin ligase enzyme that adds polyubiquitin to cdk-cyclin complex –> cyclin degrades –> signals change to anaphase
What type of protein is APC?
Mutations in it are linked to what type of cancer?
adenomatous polyposis coli = tumor suppressor
colon cancer
What does the SH2 domain on GRB-2 do?
binds to phosphorylated tyrosine residues on an RTK
What are 2 common toxins that cause p53 mutations?
activated benzopyrene in cigarette smoke and aflatoxin, a fungal metabolite in moldy grain and peanuts
What happens in the G2 phase?
DNA stability is checked
How do alkylating agents work to treat cancer?
block DNA replication
affect all phases of cell cycle
How to antimetabolites work to treat cancer?
inhibit enzymes involved in DNA synthesis
S phase
What is Erbitux?
treats colorectal cancer
mAb directed against EGF receptor that is over-expressed in colorectal cancer
What triggers metaphase to anaphase?
cyclin turnover
APC/C degrades cyclin to help do this
What is the order of the cell cycle?
G0 G1 –> S –> G2 –> M
What happens in the M phase
Mitosis
Chromosome separation
Cell division
What happens in the G1 checkpoint?
occurs in response to DNA damage
timing similar to R (2 hours before S)
What happens in hereditary retinoblastoma?
mutation/deletion of once copy of RB1 is inherited –>
cells are predisposed to be cancerous –> some mutation occurs to eliminate last good copy –> cancer
How can viruses cause cancer?
During virus replication, accidentally incorporates a human proto-oncogene into its genome –> mutation turns it into an oncogene –> virus can now transform normal cells and cause cancer
Which enzyme is missing in many somatic cells that causes their senescence?
telomerase - maintains telomere length
w/out it, telomeres shrink and cells will eventually die
What type of mutations turn proto-oncogenes into oncogenes?
gain of function mutations –>
increased expression of protein products
expression of altered protein (oncoprotein) that doesn’t respond to normal signal
What is cyclin A essential for?
so that S phase can occur
What happens in the G1 phase?
RNA and protein synthesis needed for DNA replication
What does p27 do?
Inhibits cyclin-CDK by binding to it
What do small G-proteins do, and what is their significance with cancer?
monomeric G proteins that have GTPase activity (RAS); control cell proliferation; apoptosis, and a lot of other stuff; mutations can lead to cancer
How to cytotoxic antibiotics work to treat cancer?
intercalate between bases in DNA to inhibit DNA synthesis
S phase and G2 phase
What type of protein is p53?
Tumor suppressor
What types of cancers do mutations in p53 cause?
65% of colon cancers
30-50% of breast cancers
50% of lung cancers
others
What does Herceptin do?
treats breast cancer; is a monoclonal Ab for HER2/NEU
What does E7 in HPV inhibit?
Rb
What do metastasis suppressors do?
cell adhesion proteins that prevent tumor cells from dispersing and block loss of contact inhibition
How to mitotic inhibitors work to treat cancer?
Arrest cells in mitosis during metaphase
What happens in the metaphase checkpoint?
ensures chromosomes are attached to mitotic spindle
How are gain of function mutations in proto-oncogenes passed on?
autosomal dominant
What is HER2?
Proto-oncogene that, when mutated, results in overexpression of HER2
observed in many breast cancers
What type of protein is PTEN?
Mutations in it are linked to what type of cancer?
tumor suppressor
Prostate cancer
What does WEE1 Kinase do?
Inhibits Cyclin-CDK complex by hyperphosphorylating it
What type of mutations screw up tumor suppressors?
loss of function
What happens in the S phase?
DNA Synthesis
What type of protein is retinoblastoma (Rb)?
tumor suppressor
What does cyclin E do?
gets cell from G1 to S
How are loss of function mutations in tumor suppressor genes passed on?
autosomal recessive
only need 1 good copy to function
What happens in G2 checkpoint?
Verify complete genomic duplication
What is Gleevec?
treats chronic myelogenous leukemia
binds to active site of ABL tyrosine kinase and inhibits its activity
What is the most common base change in p53 that causes cancer?
G –> T transversion
What is p21?
tumor suppressor that inhibits cyclin-CDK by keeping Rb hypophosphorylated so E2F is sequestered and can’t go into S phase
