Cell Cycle, Apoptosis, and Cancer Flashcards
G1
RNA and protein synthesis occur in response to GFs.
S
DNA is replicated. RNA and proteins continue to be syn
G2
Integrity of DNA is checked. RNA and protein synthesis continue.
M
Mitosis
G0
Cells have exited the cell cycle; they are not growing or dividing.
Restriction Point
When GFs are limited, cell cycle is stopped 2 hrs. After cells pass through, they are “GF independent”.
G1 checkpoint
Verifies integrity of DNA.
G2 checkpoint
Verifies completeness of genome.
Metaphase checkpoint
Ensures attachment of chromosomes at mitotic spindle.
Permanent cell
Remain in G0. Ex: cardiac cells, neurons, RBCs.
Stable cells
Can reenter G0 w/ help of GFs. Ex: hepatocytes, epithelial cells of renal tubules.
Labile cells
Never enter cell cycle. Constantly dividing. Ex: hair, skin, gut epithelium.
Cyclin
Protein that partially activates CDKs and direct them to target to phosphorylate. Levels of cyclins can vary during the cell cycle.
CAK
Fully activate CDKs with help of cyclins.
Cyclin D (G1)
Helps cells pass through the restriction point in late G1 phase.
Complexes: cyclin D-CDK4, cyclin D-CDK6.
Cyclin E (G1/S)
Helps cells at end of G1 to commit to DNA replication and enter S phase.
Complex: cyclin E-CDK2
Cyclin A (S)
Necessary for initiation of DNA synthesis.
Complex: cyclin A-CDK2.
Cyclins A and B (M)
Necessary for nuclear division.
Complexes: cyclin A-CDK1, cyclin B-CDK1
Inhibition of CDK (2 main inhibitors)
WEE1 kinase adds another P to CDK, rendering it inactive.
p27: causes conformational change, rendering it inactive. Regulates in G1 to S transition.
Both affect CDK’s kinase activity.
CAK and the T loop
T loop blocks active site, but is displaced when cyclin binds. CAK then phosphoryates T loop and fully activates enzyme.
WEE1 kinase
Phosphorylates roof site inhibiting CDK.
CDC25
Dephosphorylates roof site, activating CDK.
APC/C (cytosome)
Regulates progression from metaphase to anaphase via degredation. Member of ubiquitin ligase family.
p53
Transcription factor. Normally degraded by proteosome in quiescent cells.
p53 affect on damaged DNA
p53 is phosphorylated and activates stimulates transcription of genes that inhibit progression of the cell cycle. (CKI inhibit cyclin-CDK complex from binding of p21).
p53 affect on undamaged DNA
Rapidly degraded by MDM2, a ubiquitin ligase.
p21
A CKI. The major target of p53 activity.
Caspase activation
Exist as a zymogen. Must be activated to become active. Forms a small and large subunit.
APAF1 and the Intrinsic pathway
Actuve BAX self-aggregates, release cyto-c. Cyto-c and APAF1 form apoptosome, which activates caspace-9 leading to apoptosis.
Proto-oncogene
Encode proteins that encourage cell growth and division.
Oncogene
Mutated version of proto-oncogene causing increase production of altered proteins (can contribute cancer growth).
Hereditary form of Rb
Mutation or deletion of Rb1 (pt is heterozygous). cells are predispositioned for cancer. Somatic mutations eliminate last “good” copy (loss of heterozygosity).
Sporatic form of Rb
Non heridary. Requires mutation of both RB1 (2 independent mutations).
HER2
Proto-oncogene. Mutation results in overexpression. Changes Val to Glu. Receptors dimerize and TK activity is increased (doesn’t require ligand). Observed in many breast cancers.
Tumor suppressors
Repress cell cycle, promote apoptosis.
Metastasis suppressors
Prevents tumor cells from dispersing by blocking loss-of-contact inhibition.
Herceptin
Monoclonal Ab (mAb) directed against HER2/NEU epidermal GF (EGF), which has been expressed in breast cancers.
Gleevec
Binds to ABL tyrosine inase and inhibits its activity. Used for chronic myelogenous leukemia.
Myc
Helps activate CDK
BCL-2
Anti apoptotic
