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

研究成果: 雜誌貢獻文章

摘要

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.
原文英語
頁(從 - 到)1282-1297
頁數16
期刊Biochimica et Biophysica Acta - Molecular Cell Research
1866
發行號8
DOIs
出版狀態已發佈 - 八月 1 2019

指紋

Mineralocorticoid Receptors
Ubiquitin
Catenins
Aldosterone
Transcriptional Activation
Apoptosis
Sumoylation
Co-Repressor Proteins
Wnt Signaling Pathway
Transforming Growth Factors
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

引用此文

Identification of two independent SUMO-interacting motifs in Fas-associated factor 1 (FAF1) : Implications for mineralocorticoid receptor (MR)-mediated transcriptional regulation. / Wang, Chi Hsien; Hung, Pei Wen; Chiang, Chi Wu; Lombès, Marc; Chen, Chang Han; Lee, Kuen Haur; Lo, Yu Chih; Wu, Mei Hsiang; Chang, Wen Chang; Lin, Ding Yen.

於: Biochimica et Biophysica Acta - Molecular Cell Research, 卷 1866, 編號 8, 01.08.2019, p. 1282-1297.

研究成果: 雜誌貢獻文章

Wang, Chi Hsien ; Hung, Pei Wen ; Chiang, Chi Wu ; Lombès, Marc ; Chen, Chang Han ; Lee, Kuen Haur ; Lo, Yu Chih ; Wu, Mei Hsiang ; Chang, Wen Chang ; Lin, Ding Yen. / Identification of two independent SUMO-interacting motifs in Fas-associated factor 1 (FAF1) : Implications for mineralocorticoid receptor (MR)-mediated transcriptional regulation. 於: Biochimica et Biophysica Acta - Molecular Cell Research. 2019 ; 卷 1866, 編號 8. 頁 1282-1297.
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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.",
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T2 - Implications for mineralocorticoid receptor (MR)-mediated transcriptional regulation

AU - Wang, Chi Hsien

AU - Hung, Pei Wen

AU - Chiang, Chi Wu

AU - Lombès, Marc

AU - Chen, Chang Han

AU - Lee, Kuen Haur

AU - Lo, Yu Chih

AU - Wu, Mei Hsiang

AU - Chang, Wen Chang

AU - Lin, Ding Yen

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AB - 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.

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