Cell Reports : The Yu Wei/Liu Chenying team revealed the mechanism by which the aging gene SIRT2 regulates the involvement of serine synthesis pathways in tumor formation.

Metabolic reprogramming provides raw materials for the rapid proliferation and growth of cells, one of the hallmarks of tumor cells.
Unlike phosphate oxide in normal cells, tumor cells choose to consume large amounts of glucose through aerobic glycolysis to produce lactic acid and ATP, known as the Warburg effect, even when oxygen is sufficient.
these metabolic path paths, often accompanied by malignant cell transformation, and the mechanisms behind them have not yet been fully clarified.
Fudan University Yu Yu's research group has long been engaged in the study of aging-related gene SIRT family regulation tumors and other aging diseases.
previously, the team revealed the work of SIRT1 in responding to oxidative stress regulation tyrosine tRNA synthase (PNAS 2017), in which SIRT3 regulates the molecular mechanisms in which a carbon unit metabolase is involved in the development of colorectal tumors (Nature Communications 2018; Cell Death and Disease 2020).
August 11, 2020, the Yuyu Task Force of Fudan University published an article on Cell Reports Online Acetylation Phosphoglycerate dehydrogenase by disrupting the interaction of E3 liga Se RNF5 to promote breast tumorigenesis, found that SIRT2 can regulate the speed limit enzyme PHGDH in the serine synthesis pathline to prevent its E3 ubilin connection enzyme RNF5 ubimination modification and degradation.
SIRT2 and Tip60 regulate the reversible acetylation modification of PHGDH in response to glucose, PHGDH acetylation in K58 destroys the binding of the ubiganic connective enzyme RNF5 to PHGDH, thus preventing PHGDH degradation PHGDH is a speed limit enzyme in the serine synthesis pathway, its high expression is related to a variety of tumors.
the number of copies of phPGDH genes present in about 40 percent of melanoma and 6 percent of breast cancer.
, however, recent studies have shown that PHGDH is still highly expressed and promotes breast cancer without an increase in the number of copies.
suggests that in cells, in addition to an increase in the number of copies of genes, there is a mechanism that regulates the expression of PHGDH.
study by the Yuyu team found that E3 ubiquitin connective enzyme RNF5 can promote the degradation of PHGDH protein and reduce serine/glycine levels in cells through ubiquitinization.
deficiency of sesine/glycine inhibits the antioxidant and proliferating capacity of tumor cells.
SIRT2 and Tip60 regulate the reverse acetylation modification of PHGDH in response to glucose, PHGDH acetylation modification as an regulatory signal, inhibit the interaction of PHGDH-RNF5, thus promoting the accumulation of PHGDH protein in tumor cells, providing a new explanation for the high expression of PHGDH in tumor cells.
this study reveals the role of SIRT2-PHGDH regulatory axis in tumor formation and provides a theoretical basis for the development of small molecule drugs targeting SIRT2-PHGDH regulatory axis to treat tumors.
Wang Chao, Ph.D. student at Fudan University, is the first author of this paper, Yu Wei Researcher of Fudan University and Liu Chenying Associate Researcher of Xinhua Hospital affiliated with Shanghai Jiaozhou University School of Medicine are co-authors, and Professor Ling Zhiqiang of Zhejiang Cancer Hospital has provided a great deal of help to this study.
Fudan University's Yu Wei team has long been committed to deacetylase HDAC family to regulate the mechanism of aging disease research.
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