p34cdk4 is a major catalytic subunit of mammalian D-type cyclins which is expressed by a gene found in human chromosome 12q13. The cdk4 protein is constitutively expressed throughout the cell cycle and it is the assembly and accumulation of functional cdk4/cyclin D complexes which is rate limiting for the progression through the G1 phase of the cell cycle. Once the complex is formed it must be activated by the phosphorylation of threonine 172 on the cdk4 subunit, a reaction mediated by a cdk-activating kinase (CAK). Complex formation and phosphorylation are independently regulated events. The phosphorylation of the cdk4 subunit is subject to regulation of both stimulatory and inhibitory cytokine signals, thereby allowing cdk4 to function as a mid G1 checkpoint. Independent of phosphorylation, cdk4 is also regulated by the binding of p16Ink4/mts1 while in complex with cyclin D.
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