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The Yeast Hex3·Slx8 Heterodimer Is a Ubiquitin Ligase Stimulated by Substrate Sumoylation
Xie, Yang Kerscher, Oliver Kroetz, Mary B McConchie, Heather F Sung, Patrick Hochstrasser, Mark
Xie, Yang
Kerscher, Oliver
Kroetz, Mary B
McConchie, Heather F
Sung, Patrick
Hochstrasser, Mark
Abstract
Hex3 and Slx8 are Saccharomyces cerevisiae proteins with important functions in DNA damage control and maintenance of genomic stability. Both proteins have RING domains at their C termini. Such domains are common in ubiquitin and ubiquitin-like protein ligases (E3s), but little was known about the molecular functions of either protein. In this study we identified HEX3 as a high-copy suppressor of a temperature-sensitive small ubiquitin-related modifier (SUMO) protease mutant, ulp1ts, suggesting that it may affect cellular SUMO dynamics. Remarkably, even a complete deletion of ULP1 is strongly suppressed. Hex3 forms a heterodimer with Slx8. We found that the Hex3·Slx8 complex has a robust substrate-specific E3 ubiquitin ligase activity. In this E3 complex, Slx8 appears to bear the core ligase function, with Hex3 strongly enhancing its activity. Notably, SUMO attachment to a substrate stimulates its Hex3·Slx8-dependent ubiquitination, primarily through direct noncovalent interactions between SUMO and Hex3. Our data reveal a novel mechanism of substrate targeting in which sumoylation of a protein can help trigger its subsequent ubiquitination by recruiting a SUMO-binding ubiquitin ligase.
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2007-11-01
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Biology
DOI
https://doi.org/10.1074/jbc.M706025200