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BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs.

Nature | Nov 22, 2012

The differentiation of several T- and B-cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodelling. Here we report that promyelocytic leukaemia zinc finger (PLZF), the BTB-zinc finger (BTB-ZF) transcription factor directing the innate-like effector program of natural killer T-cell thymocytes, is prominently associated with cullin 3 (CUL3), an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding. PLZF transports CUL3 to the nucleus, where the two proteins are associated within a chromatin-modifying complex. Furthermore, PLZF expression results in selective ubiquitination changes of several components of this complex. CUL3 was also found associated with the BTB-ZF transcription factor BCL6, which directs the germinal-centre B cell and follicular T-helper cell programs. Conditional CUL3 deletion in mice demonstrated an essential role for CUL3 in 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 new function is essential to direct the differentiation of several T- and B-cell effector programs, and may also be involved in the oncogenic role of PLZF and BCL6 in leukaemias and lymphomas.

Pubmed ID: 23086144 RIS Download

Mesh terms: Animals | B-Lymphocytes | Cell Differentiation | Cell Line | Cullin Proteins | DNA-Binding Proteins | Kruppel-Like Transcription Factors | Mice | Protein Binding | Protein Transport | Proto-Oncogene Proteins c-bcl-6 | T-Lymphocytes | Ubiquitination | Zinc Fingers

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Associated grants

  • Agency: NIAID NIH HHS, Id: R01AI038339
  • Agency: NIGMS NIH HHS, Id: R01 GM082940
  • Agency: Howard Hughes Medical Institute, Id: R01 AI038339
  • Agency: NIAID NIH HHS, Id: 5R01GM082940
  • Agency: NIGMS NIH HHS, Id:

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