@article{28954ac4d4764c8a8070035b9dc68eae,
title = "Acetylation Stabilizes Phosphoglycerate Dehydrogenase by Disrupting the Interaction of E3 Ligase RNF5 to Promote Breast Tumorigenesis",
abstract = "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.",
author = "Chao Wang and Xingyou Wan and Tong Yu and Zhenyu Huang and Chao Shen and Qian Qi and Sheng Xiang and Xinyuan Chen and Eyal Arbely and Ling, {Zhi Qiang} and Liu, {Chen Ying} and Wei Yu",
note = "Funding Information: We thank Dr. Shimin Zhao for providing SIRT2 and acetyltransferase constructs and helping with gas chromatography-mass spectrometry (GC-MS) experiments. We thank the Molecular and Cell Biology Research (MCB) lab in the Fudan Institute of Biomedical Sciences (IBS) for helping with the GC-MS experiments and the facility center of the State Key Laboratory of Genetic Engineering for assistance in the MS-MS experiments. We appreciate Dr. Yanhui Xu from Fudan University for providing the RNF5 cDNA. This work was supported by the National Key Research and Development Program of China (grant 2016YFA0500600) and the National Natural Science Foundation of China (grant nos. 31771545, 91749120, 31821002, 81672517, and 81874177). W.Y. was supported by the China “Thousand Youth Talents” Program and the Program for Professors of Special Appointment (Eastern Scholar) at the Shanghai Institutions of Higher Learning. W.Y. C.-Y.L. and C.W. conceived the study, designed the experiments, analyzed the data, and wrote the paper. C.W. X.W. and C.S. performed the molecular cell biology experiments. C.W. Q.Q. X.C. and S.X. purified the proteins. C.W. Z.H. and T.Y. performed the IHC experiments and analyzed the clinical data. E.A. helped with the site-specific incorporation assays. Z.-Q.L. provided the clinical samples. The authors declare no competing interests. Funding Information: We thank Dr. Shimin Zhao for providing SIRT2 and acetyltransferase constructs and helping with gas chromatography-mass spectrometry (GC-MS) experiments. We thank the Molecular and Cell Biology Research (MCB) lab in the Fudan Institute of Biomedical Sciences (IBS) for helping with the GC-MS experiments and the facility center of the State Key Laboratory of Genetic Engineering for assistance in the MS-MS experiments. We appreciate Dr. Yanhui Xu from Fudan University for providing the RNF5 cDNA. This work was supported by the National Key Research and Development Program of China (grant 2016YFA0500600 ) and the National Natural Science Foundation of China (grant nos. 31771545 , 91749120 , 31821002 , 81672517 , and 81874177 ). W.Y. was supported by the China “Thousand Youth Talents” Program and the Program for Professors of Special Appointment (Eastern Scholar) at the Shanghai Institutions of Higher Learning . Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = aug,
day = "11",
doi = "10.1016/j.celrep.2020.108021",
language = "English",
volume = "32",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}
