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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number2
JournalBMC Molecular and Cell Biology
Volume25
Issue number1
DOIs
Publication statusPublished - Dec 2024

Keywords

  • FAF1
  • SAP130
  • SUMO-interacting motifs (SIMs)
  • Sumoylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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