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

被引:8
作者
Costanzo, P [1 ]
Lupo, A [1 ]
Medugno, L [1 ]
D'Agostino, P [1 ]
Zevino, C [1 ]
Izzo, P [1 ]
机构
[1] Univ Naples Federico II, Fac Med & Chirurg, Dipartimento Biochim & Biotecnol Med, I-80131 Naples, Italy
关键词
negative cis element; protein kinase C; phosphorylation; cell cycle; transcriptional regulation;
D O I
10.1016/S0014-5793(99)00775-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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. (C) 1999 Federation of European Biochemical Societies.
引用
收藏
页码:61 / 66
页数:6
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