Cell Cycle pt. 1 Flashcards
M phase
mitosis
G0 phase
quiescent, intact proliferation capacity, non-cycling
G1 phase
duration between completion of cell division and intitiation of DNA replication where cells start building mass
S phase:
DNA replication
G2 phase
duration between completion of DNA replication and initiation of cell division
positive regulators of cell cycle
cyclins and CDKs
negative regulators of cell cycle
cyclin dependent kinase inhibitors (CKIs)
Cyclin B is in
made in G2
peaks in M
stops at end of M
Nuclear D1 is in
made in G1
peaks in G1
stops in S
cyclin E is in
made in g1
peaks at Rpoint
stops in S
cyclin A is in
made in S
peaks in S
stops in G2
cyclins need CDKs because
the CDKs come in and phosphorylate the cyclins to activate them via the T loop. Need 3 P to be active
there needs to be a P on the first site and two other Ps removed from those sites by a protein dephosphatase, example is Cdc25
Kinase: Cdk1 (p34) goes with cyclin
A, B1-B2,
kinase: Cdk2 goes with cyclin
A, E
kinase: Cdk4, Cdk6 goes with cyclin
D1-D3
Function of cdk1-A, cdk1-B
triggers G2-M transition
cyclin A is made in S and destroyed in prometaphase.
cyclin B is made in S/G2 and destroyed following the completion of chromsoomes attachement to the spindle
function of Cdk2-A, E
triggers G1-S transition
function of Cdk4-D, Cdk6-D
P Rb protein in G1
triggers passage of the restriction point and cyclin E synthesis in some cell types
ExC gorwith factors control synthesis of D cyclins
Cdc25A phosphatase
substrate: Cdk1, Cdk2
functions: promotes G1 to S transition and G2 to M transition
Cdc25B phosphatase
substrate: cdk1
functions: promotes G2 to M transition
Cdc25C phosphatase
substrate: cdk1
functions: promotes G2 ro M transition, dephosphosphorylates cdk1 complexed to cyclins A and B
CKIs block the action of
CDKs
ensure tight control of the cell cycle/keep balance of division
activated upon cell cycle checkpoint activation
inactivate by inhibitor binding and phosphorylation interference
Two main types of CKI
Ink (p16, 15, 18, 19) family acting on D-CDK4/6
p57, 27, 21 family acting on the E-CDK2, A-CDK2, A-CDC2, B-CDC2
When INK4 binds to the cdk,
it twists the cdk upper lobe and blocks the cyclin binding or interferes with ATP hydrolysis
when p27 or 21 binds,
a loop binds to the upper lobe of the Cdk and blocks ATP binding (interferes with ATP, ATP can’t bind)
CKI: p21
substrate: most cdk-cyclin complexes
function: induced by p53, causes cell cycle arrest after DNA damage
binds PCNA and inhibits DNA synthesis.
promotes cell senescence and terminal differentiation
CKI: p27
substrate: most cdk-cyclin complexes
functions: cell cycle arrest in response to growth suppresors like TGF-B and in contact inhibition and differentiation
INK4: p16
substrate: cdk4, cdk6
functions: cooperates with Rb protein in growth regulation
cell-cycle arrest in sensence
altered in many cancers
overlaps with p19 an important regulator of p53 tumor supressor protein
Ras Superfamily
small GTPases activated by mitogen binding to receptor
turns on MAP kinase which makes the Myc gene
Myc gene makes Myc which is a transcription factor
Myc transcribes a bunch of proteins for cell cycle control
Myc effects
increased cyclin D, increased p27 degradation, increased E2F synthesis, Rb phosphorylation, and entry into S phase
Restriction point
between G1/S transition
unphosphorylated pRb gets P by D-CDK4
in its hypophosphorylated phase, it hits the restriction point
once it is hyperphosphorylated, it is comited to continuing through the cell cycle
this is a positive feedback loop
during the S phase know that
CDK/cyclin A is stabilizing the prereplciation complex
G2/M phase transition
cdk1 is inactive, cyclin B1 is around but not bound
cdk1 dephosphorylation kicks off the two Psand makes Cdk1 active and it binds to cyclin B1
once it forms it can go to mitosis (M phase) and be used then gets ubiquinated for degradation and inactive Cdk1 is back in g1
G1 checkpoint pathway (after DNA damage-cell needs to not replicate): slow pathway
ATM makes Mdm wtih p53
p53 makes p21
p21 inhibits cell cycle, stuck in G1
G1 checkpoint pathway (after DNA damage): fast pathway
ATM makes Chk2 which interrupts/breaks Cdc25 which inhibits cell cycle, stuck in G1
p53 is mutated in
almost every cancer
Cells stuck in the G1 checkpoint can
eventually go back into the cell cycle if they are repaired
ARP/p16 pathway (G1 checkpoint)
downstream signaling, G1 arrests via p53 and p21 or directly CDK1 p16 will prevent Rb Phosphoryaltion via inhibition of the CDK4 and CDK6 kinases
responds to dna damage and other types of damage
cells will almost never go back into cell cycle from here
G2 checkpoint: ATM
ATM makes mdm2 with p53
p53 makes p21
p21 makes cyclinB-cdk1 (phosp)
cyclin B-cdk1 is dephospho. by Cdc25 and then inhibits further progression into the cell cycle
G2 checkpoint: ATR
ATR makes chk1 and chk2 which are phosph.
cdc25 comes in a takes off the p
cyclinB-cdk1 come into play from the other pathway and the cell cycle is stopped
