Acetylation Stabilizes Phosphoglycerate Dehydrogenase by Disrupting the Interaction of E3 Ligase RNF5 to Promote Breast Tumorigenesis
Chao Wang,
Xingyou Wan,
Tong Yu,
Zhenyu Huang,
Chao Shen,
Qian Qi,
Sheng Xiang,
Xinyuan Chen,
Eyal Arbely,
Zhi-Qiang Ling,
Chen-Ying Liu,
Wei Yu
Affiliations
Chao Wang
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Xingyou Wan
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Tong Yu
Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Colorectal Cancer Research Center, Shanghai 200092, China
Zhenyu Huang
Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Colorectal Cancer Research Center, Shanghai 200092, China
Chao Shen
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Qian Qi
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Sheng Xiang
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Xinyuan Chen
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Eyal Arbely
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Zhi-Qiang Ling
Experimental Research Centre, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou 310022, China
Chen-Ying Liu
Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Colorectal Cancer Research Center, Shanghai 200092, China; Corresponding author
Wei Yu
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China; Corresponding author
Summary: Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme in the serine synthesis pathway in which it is also the rate-limiting enzyme. It is significantly upregulated in many cancers, especially breast cancer. However, the posttranslational mechanism of PHGDH upregulation in breast cancer is unknown. In this study, we find that RNF5, an E3 ubiquitin ligase, is essential for the degradation of PHGDH protein. PHGDH is degraded by RNF5 to prevent the proliferation of breast cancer cells. The acetylation of PHGDH at K58 is able to disrupt the interaction of RNF5-PHGDH and promote the proliferation of breast cancer cells. Tip60 and SIRT2 regulate the reversible acetylation modification of PHGDH in response to glucose alteration. Moreover, PHGDH is significantly upregulated in samples of human breast cancer and is associated with decreased RNF5 expression. This implies a potential therapeutic target through the interference interaction of PHGDH-RNF5 to degrade PHGDH in breast cancer.
