cell cycle Flashcards
mitogenic signals
growth factors/signaling molecules
stimulate cell division
epidermal growth factor (EGF) is an example
epidermal growth factor
a type of mitogenic signal
receptor is Her
MAP kinase cascade
GRB2 binds phosphotyrosine
GRB2 binds Sos, bringing Sos to cell membrane
Sos interacts with Ras (G-protein)
Sos promotes exchange of GDP for GTP, activating Ras
Ras activates Raf
Raf phosphorylates and activates MAP kinase kinase
MAP kinase kinase phosphorylates and activates MAP kinase
MAP kinase enters nucleus and activates genes that stimulate cell division
growth factor signal transduction
a
structure of growth factor receptor
transmembrane protein (dimer) with 3 domains: ligand binding domain transmembrane domain cytoplasmic tyrosine kinase domain
cyclin-dependent kinases (CDKs)
regulate progression through cell cycle
serine/threonine kinases
phosphorylate different protein targets
cyclins
function in complexes with CDKs synthesized at specific points in cell cycle degraded by ubiquitin-dependent proteolysis once they do their job
G1/S checkpoint
checks whether conditions are favorable for division
E2F regulates transition during early G1 phase
Rb keeps E2F inactive
mitogens stimulate transcription of cyclin D-CDK4/6
cyclin D-CDK4/6 complex phosphorylates Rb and releases E2F
E2F activates transcription of cyclin E-CDK2
cyclin E-CDK2 phosphorylates Rb making Rb phosphorylation independent of mitogens
free E2F activates transcription of genes required for DNA replication
transition to S phase (regulated by the following):
CDK2-cyclin A is inactive, inhibited by p27
cyclin E-CDK2 from late G1 phosphorylates p27, sends it for proteolysis
cyclin A-CDK2 no longer inhibited, but CDK2 must be dephosphorylated by phosphatase, then becomes activated and DNA replication can begin
G2/M checkpoint
ensures all DNA is replicated and undamaged
metaphase/anaphase transition checkpoint
evaluates whether all chromosomes are attached to mitotic spindle
DNA damage checkpoint
functions throughout cell cycle and detects damaged DNA
if damaged DNA is detected, arrests cell cycle and repairs DNA or initiates apoptosis
cell to cell interactions
interactions between neighboring cells inhibit cell division
this is called contact inhibition
cancer cells lose contact inhibition
cell to matrix interactions
interactions between cell and ECM promote cell division
phases of cell cycle
G1 growth S DNA replication G2 growth M mitosis G0 resting state/quiescence
G1 phase
period of growth
synthesis of proteins and metabolites necessary for DNA replication
S phase
DNA replication
at conclusion of S phase, each chromosome is comprised of two identical sister chromatids linked at centromere
G2 phase
second period of growth
precedes cell division (M phase)
M phase
mitosis/cell division
produces two identical daughter cells
early-response genes
a
delayed-response genes
a