Sp1 O-glycosylation leads to glucose-dependent NF-κBp65 activation

Introduction: The transcription factor NF-κB plays an important role in diabetes. The molecular mechanisms underlying the observed long-term activation of NF-κB p65 mRNA transcription in diabetes are yet unknown. Characteristics of the p65 promoter shows three binding sites for the transcription factors Sp1/Sp3, implying that these proteins might act as transactivators of p65 de novo synthesis under hyperglycemic conditions. Aims: We studied the influence of glucose-mediated posttranslational modifications of Sp1 on NF-κB p65 gene transcription to characterize the molecular mechanisms underlying p65 de novo synt…