Fem1b promotes ubiquitylation and suppresses transcriptional activity of Gli1

Andrew S. Gilder, Yong Bin Chen, Ramon J. Jackson, Jin Jiang, Joseph F. Maher

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The mammalian Fem1b gene encodes a homolog of FEM-1, a protein in the sex-determination pathway of the nematode Caenorhabditis elegans. Fem1b and FEM-1 proteins each contain a VHL-box motif that mediates their interaction with certain E3 ubiquitin ligase complexes. In C. elegans, FEM-1 negatively regulates the transcription factor TRA-1, and functions as an E3 ubiquitin ligase substrate recognition subunit to target TRA-1 for ubiquitylation. TRA-1 is homologous to the mammalian Gli1 protein, a transcription factor that mediates Hedgehog signaling as well as having Hedgehog-independent functions. Whether the interaction between nematode FEM-1 and TRA-1 proteins is conserved, between corresponding mammalian homologs, has not been reported. Herein, we show that Fem1b interacts with Gli1 within cells, and directly binds Gli1. Fem1b also promotes ubiquitylation of Gli1, suppresses transcriptional activation by Gli1, and attenuates an oncogenic Gli1 autoregulatory loop in cancer cells, all dependent on the VHL-box of Fem1b. These findings have implications for understanding the cellular functions of Fem1b, and the regulation of Gli1 oncoprotein activity.

Original languageEnglish (US)
Pages (from-to)431-436
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume440
Issue number3
DOIs
StatePublished - Oct 25 2013

Keywords

  • FEM-1
  • Fem1b
  • Gli1
  • TRA-1
  • Transcription
  • Ubiquitin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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