Protection of c-Fos from autophagic degradation by PRMT1-mediated methylation fosters gastric tumorigenesis.

Autor:	Kim E; Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea.; R&D Center, Yungjin Pharmaceutical Co, Suwon 16229, Republic of Korea., Rahmawati L; Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea.; Emergency Department, Hermina Hospital Tangkubanprahu, Malang 65119, Indonesia., Aziz N; Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea.; Pharmacy Program, Faculty of Science and Engineering, Universitas Ma Chung, Malang 65151, Indonesia., Kim HG; Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea., Kim JH; Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea., Kim KH; Proteomic Analysis Team, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea., Yoo BC; Division of Translational Science, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea., Parameswaran N; Department of Physiology and Division of Pathology, Michigan State University, East Lansing, Michigan 48824, USA., Kang JS; Department of Molecular Cell Biology, Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea., Hur H; Department of Surgery, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of Korea., Manavalan B; Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea., Lee J; Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea., Cho JY; Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea.
Jazyk:	angličtina
Zdroj:	International journal of biological sciences [Int J Biol Sci] 2023 Jul 15; Vol. 19 (12), pp. 3640-3660. Date of Electronic Publication: 2023 Jul 15 (Print Publication: 2023).
DOI:	10.7150/ijbs.85126
Abstrakt:	Both AP-1 and PRMT1 are vital molecules in variety of cellular progresssion, but the interaction between these proteins in the context of cellular functions is less clear. Gastric cancer (GC) is one of the pernicious diseases worldwide. An in-depth understanding of the molecular mode of action underlying gastric tumorigenesis is still elusive. In this study, we found that PRMT1 directly interacts with c-Fos and enhances AP-1 activation. PRMT1-mediated arginine methylation (mono- and dimethylation) of c-Fos synergistically enhances c-Fos-mediated AP-1 liveliness and consequently increases c-Fos protein stabilization. Consistent with this finding, PRMT1 knockdown decreases the protein level of c-Fos. We discovered that the c-Fos protein undergoes autophagic degradation and found that PRMT1-mediated methylation at R287 protects c-Fos from autophagosomal degradation and is linked to clinicopathologic variables as well as prognosis in stomach tumor. Together, our data demonstrate that PRMT1-mediated c-Fos protein stabilization promotes gastric tumorigenesis. We contend that targeting this modification could constitute a new therapeutic strategy in gastric cancer. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).)
Databáze:	MEDLINE
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