Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7.

Abstract:

:Timely degradation of regulatory proteins by the ubiquitin proteolytic pathway (UPP) is an established paradigm of cell cycle regulation during the G2/M and G1/S transitions. Less is known about roles for the UPP during S phase. Here we present evidence that dynamic cell cycle-dependent changes in levels of UbcH7 regulate entrance into and progression through S phase. In diverse cell lines, UbcH7 protein levels are dramatically reduced in S phase but are fully restored by G2. Knockdown of UbcH7 increases the proportion of cells in S phase and doubles the time to traverse S phase, whereas UbcH7 overexpression reduces the proportion of cells in S phase. These data suggest a role for UbcH7 targets in the completion of S phase and entry into G2. Notably, UbcH7 knockdown was coincident with elevated levels of the checkpoint kinase Chk1 but not Chk2. These results argue that UbcH7 promotes S phase progression to G2 by modulating the intra-S phase checkpoint mediated by Chk1. Furthermore, UbcH7 levels appear to be regulated by a UPP. Together the data identify novel roles for the UPP, specifically UbcH7 in the regulation of S phase transit time as well as in cell proliferation.

journal_name

Mol Biol Cell

authors

Whitcomb EA,Dudek EJ,Liu Q,Taylor A

doi

10.1091/mbc.e08-01-0036

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

1-9

issue

1

eissn

1059-1524

issn

1939-4586

pii

E08-01-0036

journal_volume

20

pub_type

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