MAT1-Modulated CAK Activity Regulates Cell Cycle G sub(1) Exit

The cyclin-dependent kinase (CDK)-activating kinase (CAK) is involved in cell cycle control, transcription, and DNA repair (E. A. Nigg, Curr. Opin. Cell. Biol. 8:312-317, 1996). However, the mechanisms of how CAK is integrated into these signaling pathways remain unknown. We previously demonstrated...

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Bibliographic Details
Published in:Molecular and cellular biology 2001-01, Vol.21 (1), p.260-270
Main Authors: Wu, L, Chen, P, Shum, CH, Chen, C, Barsky, L W, Weinberg, KI, Jong, A, Triche, T J
Format: Article
Language:English
Subjects:
CAK protein
cyclin E
cyclin-dependent kinase-activating kinase
MAT1 protein
Rb protein
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Summary:The cyclin-dependent kinase (CDK)-activating kinase (CAK) is involved in cell cycle control, transcription, and DNA repair (E. A. Nigg, Curr. Opin. Cell. Biol. 8:312-317, 1996). However, the mechanisms of how CAK is integrated into these signaling pathways remain unknown. We previously demonstrated that abrogation of MAT1 (menage a trois 1), an assembly factor and targeting subunit of CAK, induces G sub(1) arrest (L. Wu, P. Chen, J. J. Hwang, L. W. Barsky, K. I. Weinberg, A. Jong, and V. A. Starnes, J. Biol. Chem. 274:5564- 5572, 1999). This result led us to investigate how deregulation of CAK by MAT1 abrogation affects the cell cycle G sub(1) exit, a process that is regulated most closely by phosphorylation of retinoblastoma tumor suppressor protein (pRb). Using mammalian cellular models that undergo G sub(1) arrest evoked by antisense MAT1 abrogation, we found that deregulation of CAK inhibits pRb phosphorylation and cyclin E expression, CAK phosphorylation of pRb is MAT1 dose dependent but cyclin D1/CDK4 independent, and MAT1 interacts with pRb. These results suggest that CAK is involved in the regulation of cell cycle G sub(1) exit while MAT1-modulated CAK formation and CAK phosphorylation of pRb may determine the cell cycle specificity of CAK in G sub(1) progression.
ISSN:0270-7306