PKC‐dependent phosphorylation of the p97 repressor regulates the transcription of aldolase A L‐type promoter

FEBS Letters

Zevino, Chiara¹  Izzo, Paola¹  Costanzo, Paola¹  Medugno, Lina¹  Lupo, Angelo¹  D'Agostino, Paola¹ 

[1] Dipartimento di Biochimica e Biotecnologie Mediche, Facoltà di Medicina e Chirurgia, Università di Napoli ‘Federico II’, via S. Pansini 5, 80131 Naples, Italy

关键词: Negative cis element;    Protein kinase C;    Phosphorylation;    Cell cycle;    Transcriptional regulation;    CAT;    chloramphenicol acetyltransferase;    AldA-NRE;    aldolase A negative regulatory element;    EMSA;    electrophoretic mobility shift assay;    TPA;    phorbol ester 12-O-tetradecanoylphorbol 13-acetate;    H7;    1-(5-isoquinolinesulphonyl)-2-methylpiperazine;    4NPP;    4-nitrophenylphosphate;    PAP;    potato acid phosphatase;   

DOI  :  10.1016/S0014-5793(99)00775-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown