Unknown

Dataset Information

0

MTORC1 activity regulates post-translational modifications of glycine decarboxylase to modulate glycine metabolism and tumorigenesis.


ABSTRACT: Glycine decarboxylase (GLDC) is a key enzyme of glycine cleavage system that converts glycine into one-carbon units. GLDC is commonly up-regulated and plays important roles in many human cancers. Whether and how GLDC is regulated by post-translational modifications is unknown. Here we report that mechanistic target of rapamycin complex 1 (mTORC1) signal inhibits GLDC acetylation at lysine (K) 514 by inducing transcription of the deacetylase sirtuin 3 (SIRT3). Upon inhibition of mTORC1, the acetyltransferase acetyl-CoA acetyltransferase 1 (ACAT1) catalyzes GLDC K514 acetylation. This acetylation of GLDC impairs its enzymatic activity. In addition, this acetylation of GLDC primes for its K33-linked polyubiquitination at K544 by the ubiquitin ligase NF-X1, leading to its degradation by the proteasomal pathway. Finally, we find that GLDC K514 acetylation inhibits glycine catabolism, pyrimidines synthesis and glioma tumorigenesis. Our finding reveals critical roles of post-translational modifications of GLDC in regulation of its enzymatic activity, glycine metabolism and tumorigenesis, and provides potential targets for therapeutics of cancers such as glioma.

SUBMITTER: Liu R 

PROVIDER: S-EPMC8270999 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7889154 | biostudies-literature
| S-EPMC4905368 | biostudies-other
| S-EPMC7544202 | biostudies-literature
| S-EPMC2951466 | biostudies-literature
| S-EPMC8652059 | biostudies-literature
| S-EPMC5553009 | biostudies-literature
| S-EPMC7504708 | biostudies-literature
| S-EPMC7051976 | biostudies-literature
| S-EPMC3499978 | biostudies-literature
| S-EPMC7323054 | biostudies-literature