Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function

Chang-Han Chen; Hung-Wei Lin; Meng-Fang Huang; Chi-Wu Chiang; Kuen-Haur Lee; Nguyen Thanh Phuong; Zong-Yan Cai; Wen-Chang Chang; Ding-Yen Lin

doi:10.1186/s12860-023-00498-x

Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function

BMC Mol Cell Biol. 2024 Jan 4;25(1):2. doi: 10.1186/s12860-023-00498-x.

Authors

Chang-Han Chen^{1

2}, Hung-Wei Lin³, Meng-Fang Huang³, Chi-Wu Chiang⁴, Kuen-Haur Lee⁵, Nguyen Thanh Phuong³, Zong-Yan Cai³, Wen-Chang Chang^{6

7}, Ding-Yen Lin^{8

9}

Affiliations

¹ Department of Medical Research, Taichung Veterans General Hospital, Taichung, 407219, Taiwan, ROC.
² Department of Applied Chemistry, and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Nantou, 545301, Taiwan, ROC.
³ Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
⁴ Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
⁵ Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan, ROC.
⁶ Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
⁷ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei Medical University, Taipei, 11031, Taiwan, ROC.
⁸ Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 70101, Taiwan, ROC. lindy@mail.ncku.edu.tw.
⁹ Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan, ROC. lindy@mail.ncku.edu.tw.

Abstract

Background: Fas-associated factor 1 (FAF1) is a multidomain protein that interacts with diverse partners to affect numerous cellular processes. Previously, we discovered two Small Ubiquitin-like Modifier (SUMO)-interacting motifs (SIMs) within FAF1 that are crucial for transcriptional modulation of mineralocorticoid receptor. Recently, we identified Sin3A-associated protein 130 (SAP130), a putative sumoylated protein, as a candidate FAF1 interaction partner by yeast two-hybrid screening. However, it remained unclear whether SAP130 sumoylation might occur and functionally interact with FAF1.

Results: In this study, we first show that SAP130 can be modified by SUMO1 at Lys residues 794, 878 and 932 both in vitro and in vivo. Mutation of these three SUMO-accepting Lys residues to Ala had no impact on SAP130 association with Sin3A or its nuclear localization, but the mutations abrogated the association of SAP130 with the FAF1. The mutations also potentiated SAP130 trans-repression activity and attenuated SAP130-mediated promotion of cell growth. Additionally, SUMO1-modified SAP130 was less stable than unmodified SAP130. Transient transfection experiments further revealed that FAF1 mitigated the trans-repression and cell proliferation-promoting functions of SAP130, and promoted SAP130 degradation by enhancing its polyubiquitination in a sumoylation-dependent manner.

Conclusions: Together, these results demonstrate that sumoylation of SAP130 regulates its biological functions and that FAF1 plays a crucial role in controlling the SUMO-dependent regulation of transcriptional activity and protein stability of SAP130.

Keywords: FAF1; SAP130; SUMO-interacting motifs (SIMs); Sumoylation.

MeSH terms

Protein Stability
Sumoylation*
Transcription Factors* / metabolism
Ubiquitination

Substances

Transcription Factors