Phenyl hydroquinone, an Ames test-negative carcinogen, induces Hog1-dependent stress response signaling.
Recently, we have shown that phenyl hydroquinone, a hepatic metabolite of the Ames test-negative carcinogen o-phenylphenol, efficiently induced aneuploidy in Saccharomyces cerevisiae. We further found that phenyl hydroquinone arrested the cell cycle at G(1) and G(2)/M. In this study, we demonstrate that phenyl hydroquinone can arrest the cell cycle at the G(2)/M transition as a result of stabilization of Swe1 (a Wee1 homolog), probably leading to inactivation of Cdc28 (a Cdk1/Cdc2 homolog). Furthermore, Hog1 (a p38 MAPK homolog) was robustly phosphorylated by phenyl hydroquinone, which can stabilize Swe1. On the other hand, Chk1 and Rad53 were not phosphorylated by phenyl hydroquinone, indicating that the Mec1/Tel1 DNA-damage checkpoint was not functional. Mutations of swe1 and hog1 abolished phenyl hydroquinone-induced arrest at the G(2)/M transition and the cells became resistant to phenyl hydroquinone lethality and aneuploidy development. These data suggest that a phenyl hydroquinone-induced G(2)/M transition checkpoint that is activated by the Hog1-Swe1 pathway plays a role in the development of aneuploidy.
Yamamoto
Ayumi
A
Graduate School of Life Sciences, Tohoku University, Sendai, Japan. yamamot@m.tains.tohoku.ac.jp
Nunoshiba
Tatsuo
T
Umezu
Keiko
K
Enomoto
Takemi
T
Yamamoto
Kazuo
K
D000782:Aneuploidy; D001713:Biphenyl Compounds / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016195:G2 Phase; D006873:Hydroquinones / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013312:Stress, Physiological
D001713:Biphenyl Compounds; D002273:Carcinogens; D018797:Cell Cycle Proteins; D006873:Hydroquinones; D029701:Saccharomyces cerevisiae Proteins; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C066330:phenylhydroquinone; C031927:hydroquinone