Cell cycle regulation Flashcards
cyclin
activate CDKs
cyclin dependent kinase (CDK)
regulate progression through the cell cycle when active (bound to cyclin)
CDK inhibitors
bind to CDK-cyclin complex and inhibit its activity
retinoblastoma protein (Rb) role in cell cycle regulation
binds to and inhibits E2F, inhibiting cell cycle progression - cell arrests in G1 when bound
cancer associated with mutation of Rb
hereditary retinoblastoma due to one mutant Rb allele that causes defective G1 checkpoint
transcription factor p53 role in cell cycle regulation
activated by double-stranded break -> stimulates transcription of p21 -> p21 binds to and inactivates CDK-cyclin complex-> cell arrested in G1 until DNA damage repaired, or if damage is too great starts apoptosis
cancers associated with transcription factor p53
> 90% human cutaneous squamous cell carcinomas
~50% of all other human cancers
due to failure of apoptosis
Pathway for pro survival signaling via Ras-MAPK
growth factors (TGFa, EGF) stimulate RTK -> Das -> Raf -> MEK -> MEKK, MAPK, MKK -> For & Jun -> transcription, cellular growth and division
How can cancer develop from RTK pathway mutations?
abnormal Ras/MAPK signaling can increase cell proliferation
defect in apoptotic pathways
over-stimulation of pro survival pathway
Ras-GEF
active form, GEF binds Ras/GDP and accelerates replacement of GDP by GTP
Ras-GAP
GAP binds Ras/GTP and promotes GTP hydrolysis and thus deactivation
Ras-GEF
GEF (Guanine-nucleotide exchange factor)
active form, GEF binds Ras/GDP and accelerates replacement of GDP by GTP
Ras-GAP
GAP (GTPase activating protein)
GAP binds Ras/GTP and promotes GTP hydrolysis and thus deactivation
H-Ras, K-Ras, N-Ras
most common oncoprotein in cancer
normal GTP binding but no GTPase activity - remains continuously active
HER2
RTK that is over expressed in some breast cancers - usually via gene amplification that leads to having 1-2 million receptors rather than the normal 2.
