Transcriptional repression of p21((Waf1/Cip1/Sdi1)) gene by c-jun through Sp1 site.
Previously, we found that c-jun represses the tumor suppressor p21((Waf1/Cip1/Sdi1)) (p21) gene expression. In this study, we further investigated the mechanism of the inhibitory effect of c-jun on p21. After analysis of a series of deletion and point mutants of p21 promoter, we found that Sp1-3 site (-77 and -83) relative to the transcription start site played an important role for c-jun-repressing-responsive element in the p21 promoter. Both Sp1 and Sp3 transcription factors were the key factors for this event. However, the data from electrophoretic mobility shift assay indicated that c-jun did not change the Sp1 DNA-binding affinity, suggesting that additional factors may be involved in the repression of p21 by c-jun. Furthermore, c-jun could inhibit butyrate-inducing p21 gene expression through Sp1, indicating at least one common pathway whereby p21 expression is affected by c-jun and butyrate in opposing actions. Moreover, the hyperphosphorylated retinoblastoma protein (Rb) increased in c-jun expressing cells, indicating that phosphorylated Rb may play a role in regulating Sp1 to repress p21 expression. This is the first demonstration of how housekeeping factors and oncogene product counteract the function of tumor suppressor genes to control cell cycle progression.
Wang
C H
CH
Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Tsao
Y P
YP
Chen
H J
HJ
Chen
H L
HL
Wang
H W
HW
Chen
S L
SL
D001665:Binding Sites; D002087:Butyrates / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D016758:Genes, jun; D016296:Mutagenesis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism; D017384:Sequence Deletion; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism
D002087:Butyrates; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D016160:Retinoblastoma Protein; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor