roughex down-regulates G2 cyclins in G1.
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.
Thomas
B J
BJ
Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. bthomas@sunspot.nci.nih.gov
Zavitz
K H
KH
Dong
X
X
Lane
M E
ME
Weigmann
K
K
Finley
R L
RL
Brent
R
R
Lehner
C F
CF
Zipursky
S L
SL
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D015536:Down-Regulation; D004330:Drosophila / Q000166:cytology / Q000235:genetics; D029721:Drosophila Proteins; D005123:Eye / Q000166:cytology / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism
D029721:Drosophila Proteins; D005136:Eye Proteins; C088084:rux protein, Drosophila