roughex down-regulates G2 cyclins in G1.
- B J Thomas,
- K H Zavitz,
- X Dong,
- M E Lane,
- K Weigmann,
- R L Finley,
- R Brent,
- C F Lehner and
- S L Zipursky
- Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. bthomas@sunspot.nci.nih.gov
Abstract
Cell cycle arrest in G1 at the onset of patterning in the Drosophila eye is mediated by roughex. In roughex mutants, cells accumulate Cyclin A protein in early G1 and progress into S phase precociously. When Roughex is overexpressed in S/G2 cells, Cyclin A is mislocalized to the nucleus and degraded, preventing mitosis. Whereas Roughex inhibits Cyclin A accumulation, Cyclin E down-regulates Roughex protein in vivo. Roughex binds to Cyclin E and is a substrate for a Cyclin E-Cdk complex in vitro. These data argue that Roughex inhibits Cyclin A accumulation in early G1 by targeting Cyclin A for destruction. In late G1, Roughex is destabilized in a Cyclin E-dependent process, releasing Cyclin A for its role in S/G2.
Footnotes
- Copyright © Cold Spring Harbor Laboratory Press
