May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
A Role for Ubch7 in the Regulation of S Phase of the Cell Cycle
Author Affiliations & Notes
  • A. Taylor
    Nutrition &Vision Res-USDA-HNRCA, Tufts University, Boston, Massachusetts
  • E. Whitcomb
    Nutrition &Vision Res-USDA-HNRCA, Tufts University, Boston, Massachusetts
  • E. Dudek
    Nutrition &Vision Res-USDA-HNRCA, Tufts University, Boston, Massachusetts
  • Q. Liu
    Nutrition &Vision Res-USDA-HNRCA, Tufts University, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  A. Taylor, None; E. Whitcomb, None; E. Dudek, None; Q. Liu, None.
  • Footnotes
    Support  EY RO1 13250, EYRO3 14183, American Health Assistance Foundation, Johnson and Johnson Focused Giving
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3258. doi:https://doi.org/
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    • Get Citation

      A. Taylor, E. Whitcomb, E. Dudek, Q. Liu; A Role for Ubch7 in the Regulation of S Phase of the Cell Cycle. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3258. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Timely degradation of cell cycle regulatory proteins by the ubiquitin dependent proteolytic pathway (UPP) is an established paradigm of cell cycle regulation during the G2/M and G1/S transitions. Far less is known about the rules for UPP regulation during S phase. Here we present novel evidence that dynamic cell-cycle dependent regulation of levels of the ubiquitin-conjugating enzyme (Ubc) H7, regulates both entrance into S phase as well as timely progression through S phase to G2.

Methods: : We used human lens and HeLa cell lines, RNAi to suppress UbcH7 and FAX analyses to monitor cell cycle.

Results: : We showed that 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 decreases the proportion in G1. Consistently, UbcH7 over expression reduces the proportion of S phase cells while increasing the proportion of G1 cells. UbcH7 depletion doubles the time to complete S phase in synchronized cells, suggesting a role for UbcH7 targets in the completion of S phase and entry into G2. Notably, these effects of UbcH7 knockdown were coincident with elevated levels of the checkpoint kinase Chk1 and P-280 Chk1 (but not Chk2) and with attenuated levels of phosphorylated PTEN. 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 post-translational mechanisms involving the UPP.

Conclusions: : Together these data identify UbcH7 as a regulator of S phase entry and progression and suggest a new role for UbcH7 and the UPP in cell proliferation in health and disease.

Keywords: proliferation • proteolysis • cell survival 
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