The expression of antiapoptotic protein survivin is transcriptionally upregulated by DEC1 primarily through multiple sp1 binding sites in the proximal promoter.
Human differentially expressed in chondrocytes (DEC), mouse stimulated with retinoic acid and rat split and hairy related proteins constitute a structurally distinct class of the basic helix-loop-helix proteins. DEC1 is abundantly expressed in tumors and protects against apoptosis induced by serum starvation. In this study, we report that DEC1 antiapoptosis is achieved by inducing survivin, an antiapoptotic protein. In paired tumor-normal tissues, survivin and DEC1 exhibited a paralleled expression pattern. Tetracycline-induced expression of DEC1 in stable lines proportionally increased the expression of survivin. In reporter assays, DEC1 transactivated the survivin promoter but repressed the DEC2 promoter. In contrast to the repression, the activation was delayed and varied depending on serum concentrations and cycle blockers. Studies with reporter mutants located, in the survivin promoter, two Sp1 sites that supported DEC1 transactivation. Electrophoretic mobility shift assay and chromatin immunoprecipitation detected the presence of DEC1 in the survivin promoter. These findings establish that the survivin gene is a transcription target of DEC1, and induction of survivin is at least in part responsible for DEC1 antiapoptosis.
Li
Y
Y
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, 02881, USA.
Xie
M
M
Yang
J
J
Yang
D
D
Deng
R
R
Wan
Y
Y
Yan
B
B
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism* / Q000502:physiology; D000077022:Survivin; D015534:Trans-Activators / Q000502:physiology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016329:Sp1 Transcription Factor; D000077022:Survivin; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; C422085:BHLHE41 protein, human; C107489:BIRC5 protein, human; C403671:DELEC1 protein, human