A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation
TFIID—a complex of TATA-binding protein (TBP) and TBP-associated factors (TAFs)—is a central component of the Pol II promoter recognition apparatus. Recent studies have revealed significant downregulation of TFIID subunits in terminally differentiated myocytes, hepatocytes and adipocytes. Here, we r...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/08536 |
| _version_ | 1811199755373510656 |
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| author | Li Li Silvia Sanchez Martinez Wenxin Hu Zhe Liu Robert Tjian |
| author_facet | Li Li Silvia Sanchez Martinez Wenxin Hu Zhe Liu Robert Tjian |
| author_sort | Li Li |
| collection | DOAJ |
| description | TFIID—a complex of TATA-binding protein (TBP) and TBP-associated factors (TAFs)—is a central component of the Pol II promoter recognition apparatus. Recent studies have revealed significant downregulation of TFIID subunits in terminally differentiated myocytes, hepatocytes and adipocytes. Here, we report that TBP protein levels are tightly regulated by the ubiquitin-proteasome system. Using an in vitro ubiquitination assay coupled with biochemical fractionation, we identified Huwe1 as an E3 ligase targeting TBP for K48-linked ubiquitination and proteasome-mediated degradation. Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation. We found that Huwe1 activity on TBP is antagonized by the deubiquitinase USP10, which protects TBP from degradation. Thus, modulating the levels of both Huwe1 and USP10 appears to fine-tune the requisite degradation of TBP during myogenesis. Together, our study unmasks a previously unknown interplay between an E3 ligase and a deubiquitinating enzyme regulating TBP levels during cellular differentiation. |
| first_indexed | 2024-04-12T01:53:42Z |
| format | Article |
| id | doaj.art-5de445f6732045fd9420d0adc8449413 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:53:42Z |
| publishDate | 2015-09-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-5de445f6732045fd9420d0adc84494132022-12-22T03:52:52ZengeLife Sciences Publications LtdeLife2050-084X2015-09-01410.7554/eLife.08536A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiationLi Li0https://orcid.org/0000-0002-2981-6615Silvia Sanchez Martinez1Wenxin Hu2Zhe Liu3Robert Tjian4Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States; Li Ka Shing Center for Biomedical and Health Sciences, California Institute for Regenerative Medicine Center of Excellence, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesHoward Hughes Medical Institute, Janelia Research Campus, Ashburn, United StatesTranscription Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States; Li Ka Shing Center for Biomedical and Health Sciences, California Institute for Regenerative Medicine Center of Excellence, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesTFIID—a complex of TATA-binding protein (TBP) and TBP-associated factors (TAFs)—is a central component of the Pol II promoter recognition apparatus. Recent studies have revealed significant downregulation of TFIID subunits in terminally differentiated myocytes, hepatocytes and adipocytes. Here, we report that TBP protein levels are tightly regulated by the ubiquitin-proteasome system. Using an in vitro ubiquitination assay coupled with biochemical fractionation, we identified Huwe1 as an E3 ligase targeting TBP for K48-linked ubiquitination and proteasome-mediated degradation. Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation. We found that Huwe1 activity on TBP is antagonized by the deubiquitinase USP10, which protects TBP from degradation. Thus, modulating the levels of both Huwe1 and USP10 appears to fine-tune the requisite degradation of TBP during myogenesis. Together, our study unmasks a previously unknown interplay between an E3 ligase and a deubiquitinating enzyme regulating TBP levels during cellular differentiation.https://elifesciences.org/articles/08536TBPubiquitinationHuwe1USP10differentitation |
| spellingShingle | Li Li Silvia Sanchez Martinez Wenxin Hu Zhe Liu Robert Tjian A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation eLife TBP ubiquitination Huwe1 USP10 differentitation |
| title | A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation |
| title_full | A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation |
| title_fullStr | A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation |
| title_full_unstemmed | A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation |
| title_short | A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation |
| title_sort | specific e3 ligase deubiquitinase pair modulates tbp protein levels during muscle differentiation |
| topic | TBP ubiquitination Huwe1 USP10 differentitation |
| url | https://elifesciences.org/articles/08536 |
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