L55 cell division Flashcards
CDK
cyclin dependant kinases
activity depeds in Cyclin
-cyclin determines specificity
phosphorylate serine threonine residies of substrate protiens
Phase and cyclin
G1 early: D 4/6 G1 late: E 2 -dependant on external signaling by mitogens G1S : A 2 SG2: A 1 (CDC2) G2/M B 1 (CDC2) -dependant on DNA rep completion Mphase check -dependant on alignment of chromosomes
Cell cycle starts
Mitogen binds to RTK , phophorylationL via MAPK, synthesis of MYC
-myc drives expression go Cyclin D
C-CDK 4/6 first active compled
-must be exposed every time to mitogen
restriction point
sequential activity of Cyclin D-4/6 followed by Cyclin E-CDK2 allow cell to pass rest point
both work in tandem to Pohphorylate a protein called Rb
Rb allows activation of E2f
RETINOBLASTOMA: Rb -tumor suppressor
- 3rd gest month
- hyperphosphorylation does not allow Rb to bind and suppress E2F so all protiens are expressed
- GF signal increase synthesis of Cyclin D—CDK4/6
- C-CDK 4/6 begins to phos serient threonine residoes (hypophosphorylation)
- partioal active E2F allows production of Cyclin E—-CDK2
- E-CDK2 HYPERphosphorylates and completes Rb inactivation
M phase checkpoint
G2M and M phase have scheduled halts
G2-M: activation of CDK1
M and spindle: deactivation of CDK 1
MPF maturation promoting factor
-cdc2 (cell division cycle) –cyclin B complex is as a unit is called MPF
- large number of B-CDC2 (MPF) complexes have been stockpiled but are not active
- inacgtivating phophoylations of B—CDC2 during G2 ensures CDC2 activity is minimal until ready for mitosis
:ready signal”- dna synth complete, activation of CDC25-DEPHOSPHORYLATES MPF
metaphase
line up X and spindle assembly checkpoint
-all cear signal
- activates APC (anaphase promoting complex)- ubiquitin ligase
- degrades Cyclin B & cohesion (what binds chromatids together)
- cohesion is the substrate for separase (usually kep in an inactive form via binding if inhibitory subunits)
- activated destruction of inhibitory unit of separase, degrades cohesion
unexpected DNA damage
CDKi-can halt cell cycle at any phase damage is detected
INK4 group: inhibitor of CDK4 or 6
- P16 protein
- environmental stress
WAF1/CIP1 groupL inhibits all cyclin CDK’s except 4/6
- p21
- dna damage (involved p53)