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Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex

Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the... In mammalian somatic-cell cycles, progression through the G1-phase restriction point and initiation of DNA replication are controlled by the ability of the retinoblastoma tumour-suppressor protein (pRb) family to regulate the E2F/DP transcription factors 1,2 . Continuing transcription of E2F target genes beyond the G1/S transition is required for coordinating S-phase progression with cell division 3,4,5 , a process driven by cyclin-B-dependent kinase 6,7 and anaphase-promoting complex (APC)-mediated proteolysis 8 . How E2F-dependent events at G1/S transition are orchestrated with cyclin B and APC activity remains unknown. Here, using an in vivo assay to measure protein stability in real time during the cell cycle, we show that repression of E2F activity or inhibition of cyclin-A-dependent kinase in S phase triggers the destruction of cyclin B1 through the re-assembly of APC, the ubiquitin ligase that is essential for mitotic cyclin proteolysis 9 , with its activatory subunit Cdh1 (refs 10,11,12,13). Phosphorylation-deficient mutant Cdh1 or immunodepletion of cyclin A resulted in assembly of active Cdh1–APC even in S-phase cells. These results implicate an E2F-dependent, cyclin A/Cdk2-mediated phosphorylation of Cdh1 in the timely accumulation of cyclin B1 and the coordination of cell-cycle progression during the post-restriction point period. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex

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References (36)

Publisher
Springer Journals
Copyright
Copyright © 1999 by Macmillan Magazines Ltd.
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/44611
Publisher site
See Article on Publisher Site

Abstract

In mammalian somatic-cell cycles, progression through the G1-phase restriction point and initiation of DNA replication are controlled by the ability of the retinoblastoma tumour-suppressor protein (pRb) family to regulate the E2F/DP transcription factors 1,2 . Continuing transcription of E2F target genes beyond the G1/S transition is required for coordinating S-phase progression with cell division 3,4,5 , a process driven by cyclin-B-dependent kinase 6,7 and anaphase-promoting complex (APC)-mediated proteolysis 8 . How E2F-dependent events at G1/S transition are orchestrated with cyclin B and APC activity remains unknown. Here, using an in vivo assay to measure protein stability in real time during the cell cycle, we show that repression of E2F activity or inhibition of cyclin-A-dependent kinase in S phase triggers the destruction of cyclin B1 through the re-assembly of APC, the ubiquitin ligase that is essential for mitotic cyclin proteolysis 9 , with its activatory subunit Cdh1 (refs 10,11,12,13). Phosphorylation-deficient mutant Cdh1 or immunodepletion of cyclin A resulted in assembly of active Cdh1–APC even in S-phase cells. These results implicate an E2F-dependent, cyclin A/Cdk2-mediated phosphorylation of Cdh1 in the timely accumulation of cyclin B1 and the coordination of cell-cycle progression during the post-restriction point period.

Journal

Nature – Springer Journals

Published: Oct 21, 1999

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