p300-Mediated Lysine 2-Hydroxyisobutyrylation Regulates Glycolysis.

Published

Journal Article

Lysine 2-hydroxyisobutyrylation (Khib) is an evolutionarily conserved and widespread histone mark like lysine acetylation (Kac). Here we report that p300 functions as a lysine 2-hyroxyisobutyryltransferase to regulate glycolysis in response to nutritional cues. We discovered that p300 differentially regulates Khib and Kac on distinct lysine sites, with only 6 of the 149 p300-targeted Khib sites overlapping with the 693 p300-targeted Kac sites. We demonstrate that diverse cellular proteins, particularly glycolytic enzymes, are targeted by p300 for Khib, but not for Kac. Specifically, deletion of p300 significantly reduces Khib levels on several p300-dependent, Khib-specific sites on key glycolytic enzymes including ENO1, decreasing their catalytic activities. Consequently, p300-deficient cells have impaired glycolysis and are hypersensitive to glucose-depletion-induced cell death. Our study reveals an p300-catalyzed, Khib-specific molecular mechanism that regulates cellular glucose metabolism and further indicate that p300 has an intrinsic ability to select short-chain acyl-CoA-dependent protein substrates.

Full Text

Duke Authors

Cited Authors

  • Huang, H; Tang, S; Ji, M; Tang, Z; Shimada, M; Liu, X; Qi, S; Locasale, JW; Roeder, RG; Zhao, Y; Li, X

Published Date

  • May 17, 2018

Published In

Volume / Issue

  • 70 / 4

Start / End Page

  • 663 - 678.e6

PubMed ID

  • 29775581

Pubmed Central ID

  • 29775581

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2018.04.011

Language

  • eng

Conference Location

  • United States