O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth.
Oncogene
; 39(3): 560-573, 2020 01.
Article
in En
| MEDLINE
| ID: mdl-31501520
ABSTRACT
Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined. O-GlcNAcase (OGA) is an enzyme harboring O-linked ß-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities. Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2). PKM2 is dynamically O-GlcNAcylated in response to changes in glucose availability. Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT). O-GlcNAcylation inhibits PKM2 catalytic activity and thereby promotes aerobic glycolysis and tumor growth. These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thyroid Hormones
/
Carrier Proteins
/
N-Acetylglucosaminyltransferases
/
Histone Acetyltransferases
/
Hyaluronoglucosaminidase
/
Membrane Proteins
/
Antigens, Neoplasm
/
Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2020
Document type:
Article
Affiliation country: