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A more recent version of this article appeared on December 1, 2003
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Submitted on June 8, 2003
Revised on August 1, 2003
Accepted on August 1, 2003
1 Department of Medical Biochemistry & Genetics; Texas A&M University System Health Science Center, 428 Reynolds Medical Building, College Station, TX 77843-1114
* Corresponding author. E-mail address: ywjiang{at}medicine.tamu.edu.
A key question in eukaryotic differentiation is whether there are common regulators or biochemical events that are required for diverse types of differentiation or whether there is a core mechanism for differentiation. The unicellular model organism S. cerevisiae undergoes filamentous differentiation in response to environmental cues. Since conserved cell cycle regulators, the mitotic cyclin-dependent kinase Clb2/Cdc28 and its inhibitor Swe1, were found to be involved in both nitrogen starvation- and short chain alcohol-induced filamentous differentiation, they were identified as components of the core mechanism for filamentous differentiation. We report here that slowed DNA synthesis also induces yeast filamentous differentiation through conserved checkpoint proteins Mec1 and Rad53. Swe1 and Clb2 are also involved in this form of differentiation, and the core status of Swe1/Clb2/Cdc28 in the mechanism of filamentous differentiation has therefore been confirmed. Since the cAMP and filamentous MAPK pathways that mediate nitrogen starvation-induced filamentous differentiation are not required for slowed DNA synthesis-induced filamentous growth, they can therefore be excluded from the core mechanism. More significantly, slowed DNA synthesis also induces differentiation in mammalian cancer cells, and such stimulus conservation may indicate that the core mechanism for yeast filamentous differentiation is conserved in mammalian differentiation.
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