Ubiquitin Ligase Ufd2 Is Required for Efficient Degradation of Mps1 Kinase

Chang Liu,Dewald van Dyk,Vitnary Choe,Jing Yan,Shubhra Majumder,M. Costanzo,Xin Bao,Charles Boone,K. Huo,M. Winey,H. Fisk,B. Andrews,Hai Rao

Published 2011 in Journal of Biological Chemistry

ABSTRACT

Background: Ufd2 is a U-box-containing ubiquitin-protein ligase. Results: Mps1 turnover is regulated by Ufd2 in yeast and mammalian cells. Conclusion: Our study leads to novel insights into the cell cycle control and physiological significance of the Ufd2 pathway. Significance: Understanding the functions of Ufd2 will elucidate a poorly characterized pathway in proteolysis that may be crucial to unravel the mechanisms underlying human diseases. Ufd2 is a U-box-containing ubiquitylation enzyme that promotes ubiquitin chain assembly on substrates. The physiological function of Ufd2 remains poorly understood. Here, we show that ubiquitylation and degradation of the cell cycle kinase Mps1, a known target of the anaphase-promoting complex E3, require Ufd2 enzyme. Yeast cells lacking UFD2 exhibit altered chromosome stability and several spindle-related phenotypes, expanding the biological function of Ufd2. We demonstrate that Ufd2-mediated Mps1 degradation is conserved in humans. Our results underscore the significance of Ufd2 in proteolysis and further suggest that Ufd2-like enzymes regulate far more substrates than previously envisioned.

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