Identification of a functional peroxisome proliferator activated receptor response element in the 3' untranslated region of the human bcl-2 gene.
Peroxisome proliferator activated receptors are nuclear hormone receptors that regulate the expression of genes containing a peroxisome proliferator activated receptor response element. We report here that the human bcl-2 gene contains a functional peroxisome proliferator activated receptor response element in the 3' untranslated region. Peroxisome proliferator activated receptor gamma bound the human bcl-2 peroxisome proliferator activated receptor response element in gel shift assays and co-transfection of this receptor led to increased luciferase activity from a reporter plasmid containing the human bcl-2 peroxisome proliferator activated receptor response element. Examination of peroxisome proliferator activated receptor gamma-transfected cells demonstrated an increased amount of bcl-2 message compared to empty vector-transfected cells. Confocal analyses confirmed that more Bcl-2 protein was present in peroxisome proliferator activated receptor gamma-transfected cells compared to control-transfected cells. The functionality of the increased Bcl-2 protein was examined using resistance to bile salt-induced apoptosis as the endpoint. Peroxisome proliferator activated receptor gamma-transfected cells were almost twice as resistant as control-transfected cells. These data show that PPARgamma can mediate transcription of bcl-2, resulting in an increase in Bcl-2 protein and protection from apoptosis. We discuss these findings with regards to their potential implications for colon carcinogenesis.
Butts
Brent D
BD
Department of Pharmacology, University of Colorado, VAMC, Denver, CO 80220, USA.
Tran
Nhan L
NL
Briehl
Margaret M
MM
D020413:3' Untranslated Regions / Q000235:genetics*; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D019254:Genes, bcl-2 / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D008156:Luciferases