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

Taishi Yonezawa; Hirotaka Takahashi; Shiori Shikata; Tatsuya Sawasaki; Toshio Kitamura; Susumu Goyama

doi:10.1016/j.bbrc.2018.10.006

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.

Authors

Taishi Yonezawa¹, Hirotaka Takahashi², Shiori Shikata¹, Tatsuya Sawasaki², Toshio Kitamura¹, Susumu Goyama³

Affiliations

¹ Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan.
² Proteo-Science Center (PROS), Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan.
³ Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan. Electronic address: goyama@ims.u-tokyo.ac.jp.

PMID: 30309654
DOI: 10.1016/j.bbrc.2018.10.006

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