CDK4/cyclin D complex

Function: - CDK4 is the major catalytic subunit of mammalian cyclin D - assembly & accumulation of functional CDK4/cyclin-D complexes is rate limiting for progression through G1 - once formed, the CDK4/cyclin-D complex must be activated by phosphorylation of Thr172 on CDK4, a reaction catalyzed by CAK - complex formation & phosphorylation are independently regulated events - phosphorylation of CDK4 of the CDK4/cyclin-D complex is subject to regulation by both stimulatory & inhibitory cytokine signals thus allowing CDK4 to function in a mid G1 checkpoint. - CDK4 is also regulated by the binding of p16INK4A/MTS1 while in complex with cyclin D independent of phosphorylation status Expression: - CDK4 protein is constitutively expressed throughout the cell cycle - cyclin D accumulates in G1 phase of the cell cycle

General

CDK/cyclin complex serine/threonine kinase

Properties

STATE: active state SUBUNITS: cyclin-dependent kinase-4 (CDK4) STATE: active state MOTIF: Thr phosphorylation site {N-TERMINAL} Tyr phosphorylation site {N-TERMINAL} kinase domain MOTIF: ATP-binding site NAME: ATP-binding site PSTAIRE motif MOTIF-SEQUENCE: PSTAIRE Thr-phosphate binding site EFFECTOR-BOUND: cyclin D BOUND-VIA: cyclin box Thr-phosphate {T172} cyclin D MOTIF: ubiquitination site (destruction box, D-box) SITE: N-TERMINAL FOR-BINDING-OF: ubiquitin PEST region cyclin box EFFECTOR-BOUND: cyclin-dependent kinase-4 (CDK4) BOUND-VIA: binding site LXC motif FOR-BINDING-OF: retinoblastoma-associated protein

References

Cordon-Cardo AmJ Pathol 147:545 1995

Components

cyclin D cyclin-dependent kinase-4 (CDK4) or PSK-J3