USP21 modulates Goosecoid function through deubiquitination

Biosci Rep. 2019 Jul 10;39(7):BSR20182148. doi: 10.1042/BSR20182148. Print 2019 Jul 31.

Abstract

The homeobox gene Goosecoid (GSC), which is known to regulate craniofacial development, is activated by mono-ubiquitination; however, the deubiquitylase responsible for GSC deubiquitination and inhibition has yet to be identified. In the present study, we constructed the recombinant plasmid pFlag-CMV-2-GSC and the SRY (sex-determining region Y)-box 6 (Sox6) reporter gene system to identify deubiquitylases that regulate GSC expression. We demonstrate that the ubiquitin carboxyl-terminal hydrolase 21 (USP21) regulates the deubiquitination of GSC negatively, as demonstrated by its inhibition of Sox6 reporter gene transcription. USP21 interacted with GSC to promote GSC deubiquitination while having no effect on GSC protein stability. Cell viability, migration, and function in ATDC5 cells were probably influenced by USP21 through GSC. These findings suggest that USP21 modulates GSC function through deubiquitination.

Keywords: Deubiquitination; Goosecoid; Sox6 reporter gene system; USP21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Deubiquitinating Enzymes / chemistry
  • Deubiquitinating Enzymes / genetics
  • Genes, Homeobox / genetics
  • Goosecoid Protein / chemistry
  • Goosecoid Protein / genetics*
  • HEK293 Cells
  • Humans
  • Proteolysis*
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • SOXD Transcription Factors / genetics*
  • Transfection
  • Ubiquitin Thiolesterase / chemistry
  • Ubiquitin Thiolesterase / genetics*
  • Ubiquitination / genetics

Substances

  • GSC protein, human
  • Goosecoid Protein
  • Repressor Proteins
  • SOX6 protein, human
  • SOXD Transcription Factors
  • USP21 protein, human
  • Deubiquitinating Enzymes
  • Ubiquitin Thiolesterase