RNF20/40-mediated eEF1BδL monoubiquitylation stimulates transcription of heat shock-responsive genes

Suna In1, Yong-In Kim2, J Eugene Lee2

  • 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea.

Nucleic Acids Research
|January 17, 2019
PubMed

Insights

The RNF20/40 E3 ubiquitin ligase targets heat shock transcription factor eEF1BδL for monoubiquitylation. This process enhances heat shock gene transcription through increased eEF1BδL accumulation and p-TEFb recruitment.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Ubiquitin Biology

Background:

  • RNF20/40 E3 ubiquitin ligase mediates histone H2B monoubiquitylation, crucial for transcriptional regulation.
  • Observed defects in RNF20-depleted cells indicate additional RNF20/40 ubiquitylation targets beyond histone H2B.

Purpose of the Study:

  • To identify novel ubiquitylation targets of RNF20/40.
  • To elucidate the role of eEF1BδL ubiquitylation in transcriptional regulation, particularly for heat shock-responsive genes.

Main Methods:

  • Biochemically defined assays using purified factors.
  • Cell-based analyses.
  • Investigation of protein-protein interactions.

Main Results:

  • RNF20/40, with E2 enzyme RAD6, monoubiquitylates lysine 381 of heat shock transcription factor eEF1BδL.
  • Monoubiquitylation of eEF1BδL enhances its accumulation and potentiates p-TEFb recruitment to heat shock gene promoters.
  • Cooperative interactions among eEF1BδL, RNF20/40, and HSF1 synergistically enhance heat shock-responsive gene expression.

Conclusions:

  • eEF1BδL is a novel ubiquitylation target of RNF20/40.
  • RNF20/40-mediated eEF1BδL monoubiquitylation is a key mechanism for regulating heat shock-responsive gene transcription.
  • A molecular mechanism for cooperative transcription factor function in heat shock response is provided.

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