RGD Reference Report - Cdc6 protein activates p27KIP1-bound Cdk2 protein only after the bound p27 protein undergoes C-terminal phosphorylation. - Rat Genome Database

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Cdc6 protein activates p27KIP1-bound Cdk2 protein only after the bound p27 protein undergoes C-terminal phosphorylation.

Authors: Uranbileg, B  Yamamoto, H  Park, JH  Mohanty, AR  Arakawa-Takeuchi, S  Jinno, S  Okayama, H 
Citation: Uranbileg B, etal., J Biol Chem. 2012 Feb 24;287(9):6275-83. doi: 10.1074/jbc.M111.318295. Epub 2012 Jan 5.
RGD ID: 10045360
Pubmed: PMID:22223646   (View Abstract at PubMed)
PMCID: PMC3307327   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M111.318295   (Journal Full-text)

In mammalian cells Cdk2 activity during the G(1)-S transition is mainly controlled by p27(KIP1). Although the amount and subcellular localization of p27 influence Cdk2 activity, how Cdk2 activity is regulated during this phase transition still remains virtually unknown. Here we report an entirely new mechanism for this regulation. Cdc6 the AAA+ ATPase, known to assemble prereplicative complexes on chromosomal replication origins and activate p21(CIP1)-bound Cdk2, also activated p27-bound Cdk2 in its ATPase and cyclin binding motif-dependent manner but only after the p27 bound to the Cdk2 was phosphorylated at the C terminus. ROCK, which mediates a signal for cell anchorage to the extracellular matrix and activates the mTORC1 cascade as well as controls cytoskeleton assembly, was partly responsible for C-terminal phosphorylation of the p27. In vitro reconstitution demonstrated ROCK (Rho-associated kinase)-mediated phosphorylation of Cdk2-bound p27 at the C terminus and subsequent activation of the Cdk2 by Cdc6.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Cdc6  (cell division cycle 6)
Cdkn1b  (cyclin-dependent kinase inhibitor 1B)


Additional Information