Identification of two independent SUMO-interacting motifs in Fas-associated factor 1 (FAF1): Implications for mineralocorticoid receptor (MR)-mediated transcriptional regulation

Chi Hsien Wang, Pei Wen Hung, Chi Wu Chiang, Marc Lombès, Chang Han Chen, Kuen Haur Lee, Yu Chih Lo, Mei Hsiang Wu, Wen Chang Chang, Ding Yen Lin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Fas-associated factor 1 (FAF1) was originally isolated as a Fas-associated factor and was subsequently found to interact with numerous other proteins that are involved in various cellular events including Fas-mediated apoptosis, nuclear factor (NF)-κB, Wnt/β-catenin, and transforming growth factor (TGF)-β signaling pathways, mineralocorticoid receptor (MR)-mediated transactivation, and ubiquitin-dependent processes. Herein, we defined two small ubiquitin-like modifier (SUMO)-interacting motifs (SIMs) within FAF1 and demonstrated to be crucial for transcriptional modulation of the MR. Our study demonstrated that the SIMs of FAF1 do not play a significant role in regulating its subcellular localization, Fas-mediated apoptosis, or NF-κB or Wnt/β-catenin pathways. Remarkably, FAF1 interacts with the sumoylated MR and represses aldosterone-activated MR transactivation in a SIM-dependent manner. Moreover, silencing of endogenous FAF1 in cells resulted in an increase in the induction of MR target genes by aldosterone, indicating that FAF1 functions as an MR co-repressor. We further provide evidence to suggest that the mechanisms of FAF1/SIM-mediated MR transrepression involve inhibition of MR N/C interactions and promotion of MR polyubiquitination and degradation. Sumoylation has been linked to impacting of repressive properties on several transcription factors and cofactors. Our findings therefore provide mechanistic insights underlying SUMO-dependent transcriptional repression of the MR.

Original languageEnglish
Pages (from-to)1282-1297
Number of pages16
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1866
Issue number8
DOIs
Publication statusPublished - Aug 1 2019

Keywords

  • Fas-associated factor 1
  • Mineralocorticoid receptor
  • SUMO-interacting motifs
  • Ubiquitination

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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