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

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish
Article number108021
JournalCell Reports
Volume32
Issue number6
DOIs
StatePublished - 11 Aug 2020

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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