Deacetylation of Glutaminase by HDAC4 contributes to Lung Cancer Tumorigenesis.

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, GACK311Q 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.
Mesh Terms:
Acetylation, Carcinogenesis, Carcinoma, Non-Small-Cell Lung, Cell Proliferation, Cell Transformation, Neoplastic, Glutaminase, Histone Deacetylases, Humans, Lung Neoplasms, Repressor Proteins, Ubiquitination
Int J Biol Sci
Date: Jul. 23, 2022
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