Cell Cycle, Apoptosis, and Cancer Flashcards
What are the stages of the cell cycle?
G1/G0->S->G2->M
What is done during G1/G0?
G1: RNA and protein synthesis/ cell growth
G0: Cells withdrawn from cell cycle, defective cells
What happens during S phase?
DNA is synthesized and replicated to form homologs (2 chromosomes)
What happens during M phase?
Mitosis occurs: (prophase, metaphas, anaphase, telophase) nuclear division at the beginning and cell division (cytokinesis) at the end
What occurs during G2?
DNA stability is checked
What is interphase?
G1, S, and G2
What are restiction points and checkpoints and where are they located for the cell cycle?
They are a discrete timepoint where ‘errors’ are checked.
Restriction: before S phase
Checkp: After restriction before S, end of G2, beginning of Metaphase
What is the main job of restriction point before S?
If growth factors of cell are limited, restriction occurs and removed cell from cycle
What occurs at G1 checkpoint before S?
If there is DNA damage, pulls cell from cycle and trys to fix or goes to trash
What occurs at G2 checkpoint before M?
G2 verifies complete genomic duplication, if errors cell is pulled from cycle
What occurs at metaphase checkpoint during M?
This checkpoint ensures chromosomes are attached to the mitotic spindle
What does cyclin (protein) and cyclin dependent kinases do in cell proliferation?
Activated by many things, they phosphorylate retinoblastoma (Rb) which releases E2F, which is needed to enter S phase from G1.
What are cyclin E and A needed for?
E: so that cell cycle can transition from G1 to S phase
A: so that S phase can occur
Why is cyclin important to CDKs and what are their main role?
CDK without cyclin are inactive, with cyclin binded, CDKinase is activated to phosporylate substrates so cell cycle can continue/not
What is required for full activation of cyclin/CDK?
CDK-activating kinase (CAK!) (phosphorylates)
How is cyclin/cdk inhibited?
p27 and WEE1 inhibit, or cyclin cut off by proteasomes
Where can Cyclin D-CDK4 and cyclin D- CDK6 be found?
They are found in G1 and help pass cells through the restiction point
How does p27 inhibit cyclin/cdk
Binds to both and inactivates
How does WEE1 inhibit cyclin/cdk?
WEE1 inhibits by adding another phosphate to the (roof site) and inactives cdk.
how is WEE1 phosphorylation reversed?
CDC25 phosphotase
How is Cyclin S and M activity downregulated to move into anaphase?
APC (anaphase promoting complex, cyclosome), member of ubiquitin fam, is activated, ubiquinating S and M, which signals for destruction by proteosomes, CDK inactivated, moves cells to anaphase
What is p53, what activates it, and what does it activate?
p53 is the guardian of the genome, a trasncription factor.
It is activated by protein kinases (which is activated by DNA damage), and is regulated by MDM2
It activates transcription gene of p21
How is p21 important to the cell cycle?
binds to cyclin cdk to inactivate, inactivating G1 and S phase, keeping Rb active, and E2F sequestered to it
What is the extrinsic pathway for apoptosis?
Ligand binds to death receptor (FAS or TNFalpha), activates procaspase8 to active caspase-8, activates Caspases 3,6&7, APOPtosis
What is the intrinsic pathway for apoptosis?
DNA damage activates p53 & BAX/BAK, BAX makes ports which causes mito cyto C to leak out and bind APAF-1, forming Apoptosome, which activates caspase 9, activating caspases 3,6,7 and apoptosis
What is BCL2 and BAX? What happens if cancer gets a hold of these?
BCL2 inhibits apoptosis, BAX activates apoptosis. If cancer is active, will upregulated BCL2 and downregulate BAX so cancer cells survive!
What is a oncogene?
a gene that normally promotes cell cycle
What is a tumor suppressor gene and what does it do?
a gene that inhibits cell cycle, promotes apoptosis, couple DNA damage to cell cycle
what happens if a protooncogene is mutated by point mutation, deletion or translocation?
Known as “Gain of function” become oncogene which increases expression
What is an example of an oncogene, and its mutation?
HER2 receptor, a point mutation changes valine to glutamine= NEU. which allows kinase to remain active even when to ligand. results in breast cancer (Ras)
Example of a tumor suppressor gene, and mutation?
Rb, because binds E2F to stop cell division. can cause cararacts when mutated and gets ‘second hit’
What do metastasis supressors do, example?
Cell adhesion proteins
- prevent tumor cells from dispersing
- block loss of contact inhibition
- inhibit tumor metastasis
What are the steps/mutations that lead to metastasized cancer?
Loss of APC, Mutation in Ras to always be on (oncogene), loss of tumor suppressor, loss of p53 activity, metastasis :(
What are the 6 hallmarks of cancer?
- Ability to grow alone (HER2)
- Tumor suppressor failure
- Invading and metastasis
- Telomerase up activation
- Angiogenesis
- Resisting cell death from apoptosis (mutated BAX)
Describe viral oncogene to transformed cell
Protooncogene, infected by virus, attacks and hijacks cell, Virus replicates and protooncogene turns into oncogene. infects normal cell, turning to tumor cell
HPV mechanics?
E6 binds p53(loss of t sup.) , E7 binds Rb (releases E2F), activates cell cylce/proliferation
What do alkylating agents do compared to antimetabolites?
Alkylating block DNA replication
Antimetabolites inhibits S phase
What do cytotoxic antibiotics do compared to mitotic inhibitors?
Cytotoxic intercalate between DNA bases to inhibit S/G2 phase
Mitotic arrest cells in mitosis during metaphase
What do Topo I inhibitors do compared to Topo II?
Topo I inhibitors result in tangled DNA=S phase
Topo II inhibitors result in tangled DNA in G2 phase
