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Deacetylation of Glutaminase by HDAC4 contributes to Lung Cancer Tumorigenesis.

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^K311Q 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.

SUBMITTER: Wang T

PROVIDER: S-EPMC9295053 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Deacetylation of Glutaminase by HDAC4 contributes to Lung Cancer Tumorigenesis.

Wang Tao T Lu Zhuo Z Han Tianyu T Wang Yanan Y Gan Mingxi M Wang Jian-Bin JB

International journal of biological sciences 20220704 11

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 b ...[more]

PMID: 35864951

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