Work

Desuccinylation of inosine-5′-monophosphate dehydrogenase 1 by SIRT5 promotes tumor cell proliferation

Year: 2024

Type: article

Abstract: Inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the rate limiting step of de novo purine synthesis. Currently, it remains still largely unknown how this metabolic event is regulated in tumor cells. Here, we report that a deacetylase sirtuin 5 (SIRT5) may possess a regulatory effect on GMP anabolism by desuccinylating IMPDH1. We found that SIRT5 can directly interact with IMPDH1 and promotes desuccinylation on the N terminal of IMPDH1, thereby leading to increased IMPDH enzymatic activity, enhanced purine biosynthesis and promoted cell proliferation. Consistently, downregulation of SIRT5 expression results in decreased IMPDH1 activity and impaired tumor cell proliferation. Therefore, our results reveal that SIRT5-mediated IMPDH1 desuccinylation adapts purine metabolism for rapid cell growth, and could be a potential therapeutic target for tumor cell proliferation inhibition.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2024.107976

Authors: Chang Xu, Pengbo Yao, Jie Cheng, Peng Jiang

Institutions: Center for Life Sciences, Tsinghua University, Huazhong University of Science and Technology

Language: English

Topic: Biochemical and Molecular Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,800