cell cycle and cell death Flashcards
why do hereditary cancers present at earlier ages?
already at the “initiation” phase
what ways can activate pro to-oncogenes –> oncogenes? (3)
mutation
chromosomal translocation
amplification
when do all oncogenes act?
before or during G1
example of autocrine regulation of cell growth in T-cell leukemia
Over expression of interleukin-2 and interleukin-2 receptor leads to increased T-cell growth
describe Her2-Neu
breast CA cells
val- –> glu in the transmem region leads to dimerization for stability and will activate receptor without ligand present
describe EGF-ErbB
non-small cell lung CA
deletion leads to a constitutively active TKR
discuss the “Ras” mutation
reduced GTPase activity leads to more raw-GTP (active)
discuss B-Raf mutation
melanoma
B-Raf is MAP kinase Kinase, leads to increased activity
discuss bcr-abl
CML
c-abl kinase fuses with bcr gene leading to increased phosphorylation
discuss myc
neuroblastoma, b cell lymphoma
activates cyclin D and E2F
what is the consequence of TGF-b receptor mutation/mutation in smads
decreased p15 and PAI-1
what is p15 function?
inhibitor of cyclin d-CDK4,6 complexes
what is PAI-1 function?
regulation of ECM proteins, role in mets
what is the consequence of absent Rb?
E2F constantly on, does not require cyclinD-CDK4,6 complexes to activate
what is the p21 CIP family?
inhibitor of kinase activity by binding cyclin D- CDK complexes, universal
what is the INK4 family?
specific CDK inhibitors, p15 and p16
describe p16
in INK4 family
cyclin D-CDK4 inhibitor
what is p53?
check-point control protein that functions as a transcription factor
what leads to increased p53 levels?
DNA damage
what does p53 induce? (3)
expression of p21 CDK inhibitor
Bax
DNA repair enzymes
what is BRCA-1?
scaffold protein that enhances activation of p53 and regulates Wee1 kinase and CDC25 phosphatase
what type of enzyme is telomerase?
reverse transcriptase
