E3 Ubiquitin Ligase RNF31 Cooperates with DAX-1 in Transcriptional Repression of Steroidogenesis

Anna Ehrlund, Elin Holter Anthonisen, Nina Gustafsson, Nicolas Venteclef, Kirsten Robertson Remen, Anastasios E. Damdimopoulos, Anastasia Galeeva, Markku Pelto-Huikko, Enzo Lalli, Knut R. Steffensen, Jan Åke Gustafsson, Eckardt Treuter

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Genetic and experimental evidence points to a critical involvement of the atypical mammalian orphan receptor DAX-1 in reproductive development and steroidogenesis. Unlike conventional nuclear receptors, DAX-1 appears not to function as a DNA-bound transcription factor. Instead, it has acquired the capability to act as a transcriptional corepressor of steroidogenic factor 1 (SF-1). The interplay of DAX-1 and SF-1 is considered a central, presumably ligand-independent element of adrenogonadal development and function that requires tight regulation. This raises a substantial interest in identifying its modulators and the regulatory signals involved. Here, we uncover molecular mechanisms that link DAX-1 to the ubiquitin modification system via functional interaction with the E3 ubiquitin ligase RNF31. We demonstrate that RNF31 is coexpressed with DAX-1 in steroidogenic tissues and participates in repressing steroidogenic gene expression. We provide evidence for the in vivo existence of a corepressor complex containing RNF31 and DAX-1 at the promoters of the StAR and CYP19 genes. Our data suggest that RNF31 functions to stabilize DAX-1, which might be linked to DAX-1 monoubiquitination. In conclusion, RNF31 appears to be required for DAX-1 to repress transcription, provides means to regulate DAX-1 in ligand-independent ways, and emerges as a relevant coregulator of steroidogenic pathways governing physiology and disease.

Original languageEnglish (US)
Pages (from-to)2230-2242
Number of pages13
JournalMolecular and Cellular Biology
Volume29
Issue number8
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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