Format

Send to

Choose Destination
Mol Cell. 2017 Oct 19;68(2):323-335.e6. doi: 10.1016/j.molcel.2017.09.020. Epub 2017 Oct 12.

mTORC1 Phosphorylates Acetyltransferase p300 to Regulate Autophagy and Lipogenesis.

Author information

1
Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
2
National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
3
Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address: liuwei666@zju.edu.cn.

Abstract

Acetylation is increasingly recognized as one of the major post-translational mechanisms for the regulation of multiple cellular functions in mammalian cells. Acetyltransferase p300, which acetylates histone and non-histone proteins, has been intensively studied in its role in cell growth and metabolism. However, the mechanism underlying the activation of p300 in cells remains largely unknown. Here, we identify the homeostatic sensor mTORC1 as a direct activator of p300. Activated mTORC1 interacts with p300 and phosphorylates p300 at 4 serine residues in the C-terminal domain. Mechanistically, phosphorylation of p300 by mTORC1 prevents the catalytic HAT domain from binding to the RING domain, thereby eliminating intra-molecular inhibition. Functionally, mTORC1-dependent phosphorylation of p300 suppresses cell-starvation-induced autophagy and activates cell lipogenesis. These results uncover p300 as a direct target of mTORC1 and suggest that the mTORC1-p300 pathway plays a pivotal role in cell metabolism by coordinately controlling cell anabolism and catabolism.

KEYWORDS:

autophagy; cell metabolism; lipogenesis; mTORC1; p300

PMID:
29033323
DOI:
10.1016/j.molcel.2017.09.020
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center