Cell Cycle Control Systems

What controls the cell cycle?

Progression through cell cycle controlled primarily by oscillating activity of cyclin-dependent protein kinases (Cdks)

Cdk

S/T kinases that phosphorylate substrate proteins to activate a specific phase of cell cycle; Protein levels remain constant but activity changes >> dependent on cyclins

Cyclin

co-factor for Cdk enzymes; Protein levels “cycle” up and down with the cell cycle

Yeast - Cdk is called

Cdk1

Major Cell Cycle CDKs

Without cyclins, CDKs are

inactive

Cyclic Expression Patterns

Cyclin - CDK Partners

Wee1 Kinase and Cdc25 Phosphatase

Wee1

adds an inhibitory phosphate to Cdk

Cdc25

removes the inhibitory phosphate from Cdk

Active cyclin-Cdk

exhibits positive feedback loops on both

CKI KIP

inhibits Cyclin; acts as a break in the cell cycle

CIP/KIP examples and what they do

p21, p27; bind multiple cyclin-Cdk complexes that prevent activation or inhibit kinase activity

INK protein examples and what they do

p15, p16; specific for Cdk4/6 and cyclin D; bind Cdk and inhibit the binding of cyclin D

p27

growth factor withdrawal and contact inhibition

CDK Inhibitors Table

CDK Inhibitors Cycle

UPS System table - definitions

two large, complexes are primary ubiquitin ligases for cell cycle control

SCF complex – G1/S transition

APC complex – metaphase-to-anaphase transition

Anaphase Promoting Complex

securin keeps chromosomes together and separase pulls the chromosomes apart

APC and Cyclin B/CDK1

Cyclin B/CDK1 activates

APC (cdc20)

APC (cdc20) then degrades

cyclin B

APC (cdh1) persists into G1 phase and maintains

low levels of M cyclins until SCF takes over

Cyclin D and E2F/Rb System

drives the progression into S phase from G1

Rb when bound to E2F keeps E2F inactive

When Rb is P by Cdk4/cycD and Cdk2/cycE then E2F transcribes DNA