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| Genetics May (2007); 176(1):181-92 | |
| Modulation of Ubc4p-Ubc5p-mediated stress responses by the RING-finger-dependent ubiquitin-protein ligase Not4p in Saccharomyces cerevisiae- | |
| Mulder KW, Inagaki A, Cameroni E, Mousson F, Winkler GS, De Virgilio C, Collart MA, Timmers HT | |
| Department of Physiological Chemistry, University Medical Centre Utrecht, Utrecht, The Netherlands- | |
| Abstract: The Ccr4-Not complex consists of nine subunits and acts as a regulator of mRNA biogenesis in Saccharomyces cerevisiae- The human ortholog of yeast NOT4, CNOT4, displays UbcH5B-dependent ubiquitin-protein ligase -E3 ligase- activity in a reconstituted in vitro system- However, an in vivo role for this enzymatic activity has not been identified- Site-directed mutagenesis of the RING finger of yeast Not4p identified residues required for interaction with Ubc4p and Ubc5p, the yeast orthologs of UbcH5B- Subsequent in vitro assays with purified Ccr4-Not complexes showed Not4p-mediated E3 ligase activity, which was dependent on the interaction with Ubc4p- To investigate the in vivo relevance of this activity, we performed synthetic genetic array -SGA- analyses using not4Delta and not4L35A alleles- This indicates involvement of the RING finger of Not4p in transcription, ubiquitylation, and DNA damage responses- In addition, we found a phenotypic overlap between deletions of UBC4 and mutants encoding single-amino-acid substitutions of the RING finger of Not4p- Together, our results show that Not4p functions as an E3 ligase by modulating Ubc4p-Ubc5p-mediated stress responses in vivo- | |
| [PUBMED: 17513889] |   |
| Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |