Direct activation of HSP90A transcription by c-Myc contributes to c-Myc-induced transformation.
The c-myc proto-oncogene encodes a ubiquitous transcription factor involved in the control of cell growth and differentiation and implicated in inducing tumorigenesis. Understanding the function of c-Myc and its role in cancer depends upon the identification of c-Myc target genes. Heat shock protein 90 (HSP90) is involved in the folding of proteins such as signal transduction molecules (Src, Raf1, cdk4) and steroid receptors and in enhancing the activity of telomerase and nitric-oxide synthase. Here we show that c-Myc directly activates HSP90A transcription. c-Myc-mediated induction of HSP90A transcription occurs in different tissues, is independent of cell proliferation, and is mediated by a c-Myc binding site in the proximal promoter region of HSP90A gene. Overexpression of HSP90A in Rat1a cells induces transformation. Short interference RNA of HSP90A/Hsp86alpha reduces transformation activity in HeLa and RatMyc cells. These results indicate that by induction of HSP90A c-Myc may control the activity of multiple signal pathways involved in cellular transformation.
Teng
Shu-Chun
SC
Institute of Biochemistry, National Yang-Ming University, Taipei 112, Taiwan.
Chen
Yung-Yi
YY
Su
Yi-Ning
YN
Chou
Po-Chien
PC
Chiang
Yu-Chi
YC
Tseng
Shun-Fu
SF
Wu
Kou-Juey
KJ
D000362:Agar / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000378:metabolism; D003001:Cloning, Molecular; D017930:Genes, Reporter; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D020298:U937 Cells; D015854:Up-Regulation
D002843:Chromatin; D018841:HSP90 Heat-Shock Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D000362:Agar; D008156:Luciferases