Schizosaccharomyces pombe Int6 and Ras homologs regulate cell division and mitotic fidelity via the proteasome.
Yin6 is a yeast homolog of Int6, which is implicated in tumorigenesis. We show that Yin6 binds to and regulates proteasome activity. Overexpression of Yin6 strengthens proteasome function while inactivation weakens and causes the accumulation of polyubiquitinated proteins including securin/Cut2 and cyclin/Cdc13. Yin6 regulates the proteasome by preferentially interacting with Rpn5, a conserved proteasome subunit, and affecting its localization/assembly. We showed previously that Yin6 cooperates with Ras1 to mediate chromosome segregation; here, we demonstrate that Ras1 similarly regulates the proteasome via Rpn5. In yeast, human Int6 binds Rpn5 and regulates its localization. We propose that human Int6, either alone or cooperatively with Ras, influences proteasome activities via Rpn5. Inactivating Int6 can lead to accumulation of mitotic regulators affecting cell division and mitotic fidelity.
Yen
Hsueh-Chi S
HC
Department of Molecular and Cellular Biology, Breast Cancer Center, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Gordon
Colin
C
Chang
Eric C
EC
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D003001:Cloning, Molecular; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
D002352:Carrier Proteins; D039621:Eukaryotic Initiation Factor-3; D039642:Eukaryotic Initiation Factors; C117671:Moe1 protein, S pombe; D021122:Protein Subunits; D029702:Schizosaccharomyces pombe Proteins; D025801:Ubiquitin; C419775:int6 protein, S pombe; C471107:rpn501 protein, S pombe; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D019204:GTP-Binding Proteins; C492657:Ras1 protein, S pombe; D018631:ras Proteins