The BioGRID | PUBLICATION VIEW

	Sep (2007); 0:
The yeast HEX3-SLX8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylation-
Xie Y, Kerscher O, Kroetz MB, McConchie HF, Sung P, Hochstrasser M
Yale University, New Haven, CT 06511-
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 carboxyl 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 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 Hex3Slx8 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 Hex3Slx8-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-
[PUBMED: 17848550]