Abstract: Events within and transitions between the phases of the
eukaryotic cell cycle are tightly controlled by transcriptional and
post-translational processes. Prominent among them is a profound role for the
ubiquitin proteasome proteolytic pathway. The timely degradation of proteins balances
the increases in gene products dictated by... read morechanges in transcription. Of the dozens of
ubiquitin conjugating enzymes, or E2s, functions in control of the cell cycle have
been defined for only UbcH10 and Ubc3/Cdc34. Each of these E2s works primarily with
one ubiquitin ligase or E3. Here we show that another E2, UbcH7 is a regulator of S
phase of the cell cycle. Over-expression of UbcH7 delays entry into S phase whereas
depletion of UbcH7 increases the length of S phase and decreases cell proliferation.
Additionally, the level of the checkpoint kinase Chk1 increases upon UbcH7 depletion
while the level of phosphorylated PTEN decreases. Taken together, these data indicate
that the length of S phase is controlled in part by UbcH7 through a PTEN/Akt/Chk1
pathway. Potential mechanisms by which UbcH7 controls Chk1 levels both directly and
indirectly, as well as the length of S phase are discussed and additional functions
for UbcH7 are reviewed.