The ubiquitin ligase RNF38 promotes RUNX1 ubiquitination and enhances RUNX1-mediated suppression of erythroid transcription program

Biochem Biophys Res Commun. 2018 Nov 2;505(3):905-909. doi: 10.1016/j.bbrc.2018.10.006. Epub 2018 Oct 9.

Abstract

RUNX1 is a member of RUNX transcription factors and plays important roles in hematopoiesis. RUNX1 function is under the tight control through posttranslational modifications, including phosphorylation and ubiquitination. We previously developed a luminescence-based binding assay (AlphaScreen) to systematically detect RUNX1-interacting E3 ubiquitin ligases. In this study, we showed that a nuclear ubiquitin ligase RNF38 induced ubiquitination of RUNX1. RNF38-induced RUNX1 ubiquitination did not promote RUNX1 degradation, but rather stabilized RUNX1 protein. We also found that RNF38 enhanced RUNX1-mediated transcriptional repression of the erythroid master regulator KLF1 in K562 cells. Consequently, RNF38 cooperated with RUNX1 to inhibit erythroid differentiation of K562 cells. Thus, our study identified RNF38 as a novel E3 ligase that modifies RUNX1 function without inducing its degradation.

Keywords: Erythroid differentiation; KLF1; RNF38; RUNX1; Transcriptional repression; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / pharmacology*
  • Cell Differentiation
  • Core Binding Factor Alpha 2 Subunit / drug effects
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Erythroid Cells / cytology
  • Erythroid Cells / drug effects
  • Humans
  • K562 Cells
  • Kruppel-Like Transcription Factors
  • Protein Stability / drug effects
  • Ubiquitin-Protein Ligases / pharmacology
  • Ubiquitination / drug effects*

Substances

  • Carrier Proteins
  • Core Binding Factor Alpha 2 Subunit
  • Kruppel-Like Transcription Factors
  • RNF38 protein, human
  • erythroid Kruppel-like factor
  • Ubiquitin-Protein Ligases