The SUMOylation of zinc-fingers and homeoboxes 1 (ZHX1) by Ubc9 regulates its stability and transcriptional repression activity

J Cell Biochem. 2013 Oct;114(10):2323-33. doi: 10.1002/jcb.24579.

Abstract

Zinc-fingers and homeoboxes protein 1 (ZHX1) belongs to the ZF (zinc-fingers) class of homeodomain transcription factors, and its function remains largely unknown. ZHX1 has been previously found to interact with the activation domain of the nuclear factor Y subunit A (NFYA) and to have a transcriptional repression activity. Here, we report that the SUMO-E2 conjugating enzyme Ubc9 was identified to interact with ZHX1 by an interaction screen using a yeast two-hybrid system. This interaction was confirmed by co-immunoprecipitation and co-localization assays. Further study showed that ZHX1 is SUMOylated by Ubc9 with SUMO1 at the sites K159, K454, and K626. Furthermore, we demonstrated that the SUMOylation of ZHX1 regulated the stability, ubiquitination and transcriptional activity of ZHX1.

Keywords: SUMO; SUMOYLATION; TRANSCRIPTIONAL ACTIVITY; ZHX1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Protein Binding
  • Sumoylation
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Two-Hybrid System Techniques
  • Ubiquitin-Conjugating Enzyme UBC9
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism*

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • ZHX1 protein, human
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Conjugating Enzyme UBC9