Deacetylation of Glutaminase by HDAC4 Contributes to Lung Cancer Tumorigenesis

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2022 Jul 22

PMID 35864951

Authors

Tao Wang

Zhuo Lu

Tianyu Han

Yanan Wang

Mingxi Gan

Jian-Bin Wang

Affiliations

Soon will be listed here.

Abstract

Inhibiting cancer metabolism via glutaminase (GAC) is a promising strategy to disrupt tumor progression. However, mechanism regarding GAC acetylation remains mostly unknown. In this study, we demonstrate that lysine acetylation is a vital post-translational modification that inhibits GAC activity in non-small cell lung cancer (NSCLC). We identify that Lys311 is the key acetylation site on GAC, which is deacetylated by HDAC4, a class II deacetylase. Lys311 acetylation stimulates the interaction between GAC and TRIM21, an E3 ubiquitin ligase of the tripartite motif (TRIM) family, therefore promoting GAC K63-linked ubiquitination and inhibiting GAC activity. Furthermore, GAC mutation in A549 cells decreases cell proliferation and alleviates tumor malignancy. Our findings reveal a novel mechanism of GAC regulation by acetylation and ubiquitination that participates in non-small cell lung cancer tumorigenesis.

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