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BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs
The differentiation of several T and B cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodeling. We report that PLZF, the BTB-ZF transcription factor directing the innate-like effector program of NKT thymocytes (1,2) was promi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504649/ https://www.ncbi.nlm.nih.gov/pubmed/23086144 http://dx.doi.org/10.1038/nature11548 |
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author | Mathew, Rebecca Seiler, Michael P. Scanlon, Seth T. Mao, Aiping Constantinides, Michael G. Bertozzi-Villa, Clara Singer, Jeffrey D. Bendelac, Albert |
author_facet | Mathew, Rebecca Seiler, Michael P. Scanlon, Seth T. Mao, Aiping Constantinides, Michael G. Bertozzi-Villa, Clara Singer, Jeffrey D. Bendelac, Albert |
author_sort | Mathew, Rebecca |
collection | PubMed |
description | The differentiation of several T and B cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodeling. We report that PLZF, the BTB-ZF transcription factor directing the innate-like effector program of NKT thymocytes (1,2) was prominently associated with cullin 3 (Cul3), an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding (3–7). PLZF transported Cul3 to the nucleus where the two proteins were associated within a chromatin modifying complex. Furthermore, PLZF expression resulted in selective changes of ubiquitination of multiple components of this complex. Cul3 was also found associated with another BTB-ZF transcription factor, Bcl6, which directs the B cell germinal center and the T follicular helper programs. Conditional deletion in mice demonstrated an essential role of Cul3 for the development of PLZF- and Bcl6-dependent lineages. We conclude that distinct lineage-specific BTB-ZF transcription factors recruit Cul3 to alter the ubiquitination pattern of their associated chromatin modifying complex. We propose that this novel function is essential to direct the differentiation of several T and B lymphocyte effector programs, and may also be involved in the oncogenic role of PLZF and Bcl6 in leukemias and lymphomas (8,9). |
format | Online Article Text |
id | pubmed-3504649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-35046492013-05-22 BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs Mathew, Rebecca Seiler, Michael P. Scanlon, Seth T. Mao, Aiping Constantinides, Michael G. Bertozzi-Villa, Clara Singer, Jeffrey D. Bendelac, Albert Nature Article The differentiation of several T and B cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodeling. We report that PLZF, the BTB-ZF transcription factor directing the innate-like effector program of NKT thymocytes (1,2) was prominently associated with cullin 3 (Cul3), an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding (3–7). PLZF transported Cul3 to the nucleus where the two proteins were associated within a chromatin modifying complex. Furthermore, PLZF expression resulted in selective changes of ubiquitination of multiple components of this complex. Cul3 was also found associated with another BTB-ZF transcription factor, Bcl6, which directs the B cell germinal center and the T follicular helper programs. Conditional deletion in mice demonstrated an essential role of Cul3 for the development of PLZF- and Bcl6-dependent lineages. We conclude that distinct lineage-specific BTB-ZF transcription factors recruit Cul3 to alter the ubiquitination pattern of their associated chromatin modifying complex. We propose that this novel function is essential to direct the differentiation of several T and B lymphocyte effector programs, and may also be involved in the oncogenic role of PLZF and Bcl6 in leukemias and lymphomas (8,9). 2012-10-21 2012-11-22 /pmc/articles/PMC3504649/ /pubmed/23086144 http://dx.doi.org/10.1038/nature11548 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Mathew, Rebecca Seiler, Michael P. Scanlon, Seth T. Mao, Aiping Constantinides, Michael G. Bertozzi-Villa, Clara Singer, Jeffrey D. Bendelac, Albert BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs |
title | BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs |
title_full | BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs |
title_fullStr | BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs |
title_full_unstemmed | BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs |
title_short | BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs |
title_sort | btb-zf factors recruit the e3 ligase cullin 3 to regulate lymphoid effector programs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504649/ https://www.ncbi.nlm.nih.gov/pubmed/23086144 http://dx.doi.org/10.1038/nature11548 |
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