RNF20/40-mediated eEF1B?L monoubiquitylation stimulates transcription of heat shock-responsive genes.
RNF20/40 E3 ubiquitin ligase-mediated histone H2B monoubiquitylation plays important roles in many cellular processes, including transcriptional regulation. However, the multiple defects observed in RNF20-depleted cells suggest additional ubiquitylation targets of RNF20/40 beyond histone H2B. Here, using biochemically defined assays employing purified factors and cell-based analyses, we demonstrate that RNF20/40, in ... conjunction with its cognate E2 ubiquitin-conjugating enzyme RAD6, monoubiquitylates lysine 381 of eEF1B?L, a heat shock transcription factor. Notably, monoubiquitylation of eEF1B?L increases eEF1B?L accumulation and potentiates recruitment of p-TEFb to the promoter regions of heat shock-responsive genes, leading to enhanced transcription of these genes. We further demonstrate that cooperative physical interactions among eEF1B?L, RNF20/40, and HSF1 synergistically promote expression of heat shock-responsive genes. In addition to identifying eEF1B?L as a novel ubiquitylation target of RNF20/40 and elucidating its function, we provide a molecular mechanism for the cooperative function of distinct transcription factors in heat shock-responsive gene transcription.
Mesh Terms:
Animals, Gene Expression Regulation, HEK293 Cells, Heat-Shock Response, Humans, Peptide Elongation Factor 1, Protein Binding, Protein Multimerization, Sf9 Cells, Spodoptera, Transcription, Genetic, Ubiquitin-Protein Ligases, Ubiquitination
Animals, Gene Expression Regulation, HEK293 Cells, Heat-Shock Response, Humans, Peptide Elongation Factor 1, Protein Binding, Protein Multimerization, Sf9 Cells, Spodoptera, Transcription, Genetic, Ubiquitin-Protein Ligases, Ubiquitination
Nucleic Acids Res.
Date: Dec. 08, 2018
PubMed ID: 30649429
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