O-Linked N-acetylglucosaminylation of Sp1 interferes with Sp1 activation of glycolytic genes.
Glycolysis, the primary pathway metabolizing glucose for energy production, is connected to the hexosamine biosynthetic pathway (HBP) which produces UDP-N-acetylglucosamine (UDP-GlcNAc), a GlcNAc donor for O-linked GlcNAc modification (O-GlcNAc), as well as for traditional elongated glycosylation. Thus, glycolysis and O-GlcNAc are intimately associated. The present study reports the transcriptional activation of glycolytic genes by the transcription factor Sp1 and the O-GlcNAc-mediated suppression of Sp1-dependent activation of glycolytic genes. O-GlcNAc-deficient mutant Sp1 stimulated the transcription of nine glycolytic genes and cellular production of pyruvate, the final product of glycolysis, to a greater extent than wild-type Sp1. Consistently, this mutant Sp1 increased the protein levels of the two key glycolytic enzymes, phosphofructokinase (PFK) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), to a greater extent than wild-type Sp1. Finally, the mutant Sp1 occupied GC-rich elements on PFK and GAPDH promoters more efficiently than wild-type Sp1. These results suggest that O-GlcNAcylation of Sp1 suppresses Sp1-mediated activation of glycolytic gene transcription.
David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 609, Rochester, NY 14642, United States.
Kihong
K
Lim
Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, 86 Asanbyeoungwon-gil, Songpa-gu, Seoul 138-736, Republic of Korea.
Bo Hyun
BH
Yoon
Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, 86 Asanbyeoungwon-gil, Songpa-gu, Seoul 138-736, Republic of Korea. Electronic address: chhoonha@amc.seoul.kr.
Chang Hoon
CH
Ha
D001483:Base Sequence; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006019:Glycolysis; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D025221:Phosphofructokinases / Q000235:genetics; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000235:genetics / Q000378:metabolism*
D016329:Sp1 Transcription Factor; D014537:Uridine Diphosphate N-Acetylglucosamine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D025221:Phosphofructokinases
Glycolysis; O-GlcNAc; Sp1; Transcription