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STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites
The yeast transcription factor MATα2 (α2) is a short-lived protein known to be ubiquitylated by two distinct pathways, one involving the ubiquitin-conjugating enzymes (E2s) Ubc6 and Ubc7 and the ubiquitin ligase (E3) Doa10 and the other operating with the E2 Ubc4 and the heterodimeric E3 Slx5/Slx8....
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591686/ https://www.ncbi.nlm.nih.gov/pubmed/26246605 http://dx.doi.org/10.1091/mbc.E15-06-0436 |
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author | Hickey, Christopher M. Hochstrasser, Mark |
author_facet | Hickey, Christopher M. Hochstrasser, Mark |
author_sort | Hickey, Christopher M. |
collection | PubMed |
description | The yeast transcription factor MATα2 (α2) is a short-lived protein known to be ubiquitylated by two distinct pathways, one involving the ubiquitin-conjugating enzymes (E2s) Ubc6 and Ubc7 and the ubiquitin ligase (E3) Doa10 and the other operating with the E2 Ubc4 and the heterodimeric E3 Slx5/Slx8. Although Slx5/Slx8 is a small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligase (STUbL), it does not require SUMO to target α2 but instead directly recognizes α2. Little is known about the α2 determinants required for its Ubc4- and STUbL-mediated degradation or how these determinants substitute for SUMO in recognition by the STUbL pathway. We describe two distinct degradation elements within α2, both of which are necessary for α2 recognition specifically by the Ubc4 pathway. Slx5/Slx8 can directly ubiquitylate a C-terminal fragment of α2, and mutating one of the degradation elements impairs this ubiquitylation. Surprisingly, both degradation elements identified here overlap specific interaction sites for α2 corepressors: the Mcm1 interaction site in the central α2 linker and the Ssn6 (Cyc8) binding site in the α2 homeodomain. We propose that competitive binding to α2 by the ubiquitylation machinery and α2 cofactors is balanced so that α2 can function in transcription repression yet be short lived enough to allow cell-type switching. |
format | Online Article Text |
id | pubmed-4591686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-45916862015-12-16 STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites Hickey, Christopher M. Hochstrasser, Mark Mol Biol Cell Articles The yeast transcription factor MATα2 (α2) is a short-lived protein known to be ubiquitylated by two distinct pathways, one involving the ubiquitin-conjugating enzymes (E2s) Ubc6 and Ubc7 and the ubiquitin ligase (E3) Doa10 and the other operating with the E2 Ubc4 and the heterodimeric E3 Slx5/Slx8. Although Slx5/Slx8 is a small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligase (STUbL), it does not require SUMO to target α2 but instead directly recognizes α2. Little is known about the α2 determinants required for its Ubc4- and STUbL-mediated degradation or how these determinants substitute for SUMO in recognition by the STUbL pathway. We describe two distinct degradation elements within α2, both of which are necessary for α2 recognition specifically by the Ubc4 pathway. Slx5/Slx8 can directly ubiquitylate a C-terminal fragment of α2, and mutating one of the degradation elements impairs this ubiquitylation. Surprisingly, both degradation elements identified here overlap specific interaction sites for α2 corepressors: the Mcm1 interaction site in the central α2 linker and the Ssn6 (Cyc8) binding site in the α2 homeodomain. We propose that competitive binding to α2 by the ubiquitylation machinery and α2 cofactors is balanced so that α2 can function in transcription repression yet be short lived enough to allow cell-type switching. The American Society for Cell Biology 2015-10-01 /pmc/articles/PMC4591686/ /pubmed/26246605 http://dx.doi.org/10.1091/mbc.E15-06-0436 Text en © 2015 Hickey and Hochstrasser. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Hickey, Christopher M. Hochstrasser, Mark STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites |
title | STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites |
title_full | STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites |
title_fullStr | STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites |
title_full_unstemmed | STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites |
title_short | STUbL-mediated degradation of the transcription factor MATα2 requires degradation elements that coincide with corepressor binding sites |
title_sort | stubl-mediated degradation of the transcription factor matα2 requires degradation elements that coincide with corepressor binding sites |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591686/ https://www.ncbi.nlm.nih.gov/pubmed/26246605 http://dx.doi.org/10.1091/mbc.E15-06-0436 |
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