期刊
ONCOGENE
卷 21, 期 24, 页码 3898-3908出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1205483
关键词
bcl-2; lymphoma; transcription; NF-kappa B
资金
- NCI NIH HHS [CA 56764] Funding Source: Medline
The t(14;18) translocation, which is characteristic of follicular lymphoma, results in the overexpression of the bcl-2 gene dependent upon regulatory elements within the bcl-2 5' flanking region and the immunoglobulin heavy chain gene enhancers. Conflicting evidence exists on the effects of NF-kappaB expression on Bel-2 levels in different cell types. Lymphoma cells with the t(141;18) translocation show high levels of nuclear NF-kappaB proteins. We observed decreased levels of endogenous Bcl-2 when the IkappaBchi-super-repressor was expressed in a t(14;18) cell line. Deletion analysis of the bcl-2 promoter indicated that the repressive effect of the IkappaBalpha-super-repressor occurred through a region that contained no NF-kappaB consensus sequences. This highly active region contained a c-AMP response element (CRE) and several Sp1 binding sites. Chromatin immunoprecipitation assays with antibodies specific for the NF-kappaB and CREB/ATF family members, as well as Sp1, resulted in the isolation of this IkappaBalpha-super-repressor responsive region of the bcl-2 promoter. Mutation of the CRE and the two Sp1 sites in different combinations in bel-2 reporter constructs resulted in the loss of bcl-2 promoter repression by the IkappaBalpha-super-repressor. We therefore conclude that the activation of bcl-2 by NF-kappaB in t(14;18) lymphoma cells is mediated through the CRE and Sp1 binding sites.
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