ISLET-SPECIFIC PROTEINS INTERACT WITH THE INSULIN-RESPONSE ELEMENT OF THE GLUCAGON GENE

被引:51
作者
PHILIPPE, J [1 ]
MOREL, C [1 ]
CORDIERBUSSAT, M [1 ]
机构
[1] UNIV GENEVA,SCH MED,CTR MED UNIV,DEPT MED,CH-1211 GENEVA 4,SWITZERLAND
关键词
D O I
10.1074/jbc.270.7.3039
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
Glucagon gene expression is negatively regulated by insulin at the transcriptional level. G3, a DNA control element located in the 5'-flanking sequence of the rat glucagon gene mediates the inhibition of transcription, which occurs in response to insulin. We show here that two islet-specific protein complexes C1A and C1B, bind to the A domain of G3, which is critical for the insulin response. These two complexes bind to overlapping sequences of the A domain and display Very similar binding specificities. Point mutations in the A domain that affect binding of C1A and C1B result in both decreased G3 enhancer activity and insulin-mediated inhibitory effects with a close correlation between diminution of binding and function. One of the two complexes, C1A, is similar or identical to B1, a protein complex interacting with the upstream promoter element of the glucagon gene, G(1), implicated in the A cell-specific expression of the glucagon gene. Our data indicate that islet-specific proteins are involved in glucagon gene regulation by insulin.
引用
收藏
页码:3039 / 3045
页数:7
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