O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1.

The human epigenetic cell-cycle regulator HCF-1 undergoes an unusual proteolytic maturation process resulting in stably associated HCF-1(N) and HCF-1(C) subunits that regulate different aspects of the cell cycle. Proteolysis occurs at six centrally located HCF-1(PRO)-repeat sequences and is important for activation of HCF-1(C)-subunit functions in M phase progression. We show here that the HCF-1(PRO) repeat is recognized by O-linked β-N-acetylglucosamine transferase (OGT), which both O-GlcNAcylates the HCF-1(N) subunit and directly cleaves the HCF-1(PRO) repeat.

Pharmacogenetic interaction between paraoxonase-1 gene promoter polymorphism C-107T and statin.

Objective: The aims of this study were to compare the impact of transcription factors, together with statin, on the paraoxonase promoter alleles defined by the C(-107T) polymorphism and to more clearly define regions of the paraoxonase promoter implicated in the actions of transcription factors.

Methods: Expression studies of promoter alleles were performed with reporter gene cassettes transfected into HepG2 cells, complemented by nuclease protection assays, electrophoretic mobility shift assays and statin therapy in patients.

Results: One region only of the minimal promoter fragment that up-regulates activity was protected by transcription factors and nuclear extracts.

Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2.

Background: The HDL-associated enzyme paraoxonase protects LDLs from oxidative stress. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) appear to favorably influence the atherosclerotic process by different mechanisms. The present study examined the influence of simvastatin on paraoxonase expression and serum paraoxonase levels.