Identification of c-myc as a down-stream target for pituitary tumor-transforming gene.
Pituitary tumor-transforming gene (PTTG) encodes a protein implicated in cellular transformation and transcriptional regulation. To identify downstream target genes, I established cell lines with tightly regulated inducible expression of PTTG. DNA arrays were used to analyze gene expression profiles after PTTG induction. I identified c-myc oncogene as a major PTTG target. Induction of PTTG resulted in increased cell proliferation through activation of c-myc. I showed that PTTG activates c-myc transcription in transfected cells. PTTG binds to c-myc promoter near the transcription initiation site in a protein complex containing the upstream stimulatory factor (USF1). I have defined the PTTG DNA-binding site and mapped PTTG DNA binding domain to a region between amino acids 61 and 118. Furthermore, I demonstrated that PTTG DNA binding is required for its transcriptional activation function. These results definitively established the role of PTTG as a transcription activator and indicate that PTTG is involved in cellular transformation and tumorigenesis through activation of c-myc oncogene.
Pei
L
L
Division of Endocrinology and Metabolism, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 90048, USA. pei@cshs.org
D001665:Binding Sites; D002455:Cell Division; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016259:Genes, myc; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic; D064249:Securin; D014157:Transcription Factors / Q000502:physiology; D014162:Transfection; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D064249:Securin; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C578002:pituitary tumor-transforming protein 1, human; D004247:DNA