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J Biol Chem, Vol. 273, Issue 8, 4666-4671, February 20, 1998
§ and
From the Progression through G2/M of the mammalian cell
division cycle requires the coordinated expression of many gene
products, but little is known of the transcriptional regulators
involved. Schizosaccharomyces pombe Cdc5 is a putative
transcription factor implicated in G2/M transit. We recently identified
a cDNA encoding a putative human transcription factor, now
designated human Cdc5 (hCdc5), with homology to S. pombe
Cdc5. Widespread expression of hCdc5 in human tissues and homology with
expressed sequences in other eukaryotes suggested an evolutionarily
conserved general function. Nuclear import of hCdc5 upon serum
stimulation of mammalian cells suggested a possible role in cell
proliferation. We now report that overexpression of hCdc5 in mammalian
cells shortened G2 and reduced cell size. A dominant negative mutant of
hCdc5 lacking the carboxyl-terminal activation domain slowed G2
progression and delayed entry into mitosis. Thus, hCdc5 is the first
transcriptional regulator shown to affect G2 progression and mitotic
entry in mammalian cells.
Cardiovascular Research Institute and
Departments of § Pediatrics and Medicine and Cellular
and Molecular Pharmacology, University of California,
San Francisco, California 94143
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