PKC-dependent phosphorylation of the p97 repressor regulates the transcription of aldolase A L-type promoter.
Expression of mouse aldolase A L-type mRNA is negatively modulated by a cis element (AldA-NRE), located within the aldolase A distal promoter (pL). AldA-NRE interacts with a 97-kDa repressor protein (p97), which binds DNA in a cell cycle-dependent manner. We demonstrate that the binding between AldA-NRE and p97 decreases during differentiation of human Caco-2 cells and is inversely correlated with L-type mRNA expression. Phosphorylation of the p97 repressor weakened its DNA binding activity in differentiated Caco-2 cells, while dephosphorylation enhanced the binding in proliferating cells. Stimulation of protein kinase C (PKC) in vivo decreased the binding of p97 to AldA-NRE and stimulated transcription, while inhibition of PKC stimulated p97 binding and downregulated transcription. These findings suggest that PKC is a mediator of the binding and silencing function of the p97/AldA-NRE repressor complex.
Dipartimento di Biochimica e Biotecnologie Mediche, Facoltà di Medicina e Chirurgia, Università di Napoli Federico II, Naples, Italy.
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D016475:3T3 Cells; D000818:Animals; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009687:Nuclear Proteins / Q000737:chemistry; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000737:chemistry*; D013997:Time Factors; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D011493:Protein Kinase C; D005634:Fructose-Bisphosphate Aldolase