Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function
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 modula...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Molecular and Cell Biology |
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| Online Access: | https://doi.org/10.1186/s12860-023-00498-x |
| _version_ | 1797362767098806272 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chang-Han Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T16:12:12Z |
| format | Article |
| id | doaj.art-425a48c56ec8479ab4f6de66536bde33 |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-03-08T16:12:12Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-425a48c56ec8479ab4f6de66536bde332024-01-07T12:53:34ZengBMCBMC Molecular and Cell Biology2661-88502024-01-0125111610.1186/s12860-023-00498-xSumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor functionChang-Han Chen0Hung-Wei Lin1Meng-Fang Huang2Chi-Wu Chiang3Kuen-Haur Lee4Nguyen Thanh Phuong5Zong-Yan Cai6Wen-Chang Chang7Ding-Yen Lin8Department of Medical Research, Taichung Veterans General HospitalDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityInstitute of Molecular Medicine, College of Medicine, National Cheng Kung UniversityInstitute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical UniversityDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityDepartment of Pharmacology, College of Medicine, National Cheng Kung UniversityDepartment of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung UniversityAbstract 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.https://doi.org/10.1186/s12860-023-00498-xSAP130FAF1SumoylationSUMO-interacting motifs (SIMs) |
| spellingShingle | 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 Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function BMC Molecular and Cell Biology SAP130 FAF1 Sumoylation SUMO-interacting motifs (SIMs) |
| title | Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function |
| title_full | Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function |
| title_fullStr | Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function |
| title_full_unstemmed | Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function |
| title_short | Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function |
| title_sort | sumoylation of sap130 regulates its interaction with faf1 as well as its protein stability and transcriptional repressor function |
| topic | SAP130 FAF1 Sumoylation SUMO-interacting motifs (SIMs) |
| url | https://doi.org/10.1186/s12860-023-00498-x |
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