Cloning and characterization of a functional promoter of the human SOCS-3 gene.
SOCS-3 is a member of a newly discovered protein family that inhibits LIF-activated Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling in a negative auto-regulatory manner. In this study, we have cloned and characterized the promoter region of the human SOCS-3 gene. This region is approximately 1.1 kbp in length and consists of two putative STAT-binding elements, a G-rich element, and a putative TATA box. These elements are highly conserved in both murine and rat SOCS-3 promoters. Functional analysis of this region shows that the whole fragment (approximately 1.1 kbp) has high basal promoter activity and is responsive to growth factors. We also found that the wild type SOCS-3 promoter construct has significantly greater activity in non-small-cell lung cancer cell lines than in normal cells in accordance with STAT3 disregulation in these cells. Cloning of the human SOCS-3 promoter should help uncover mechanisms of regulation of the JAK-STAT pathway in human cancer.
He
Biao
B
Department of Surgery, Thoracic Oncology Laboratory, Comprehensive Cancer Center, University of California, 1600 Divisadero St., C322C, Box 1674, San Francisco, CA 94115, USA.
You
Liang
L
Uematsu
Kazutsugu
K
Matsangou
Maria
M
Xu
Zhidong
Z
He
Miao
M
McCormick
Frank
F
Jablons
David M
DM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D017930:Genes, Reporter; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6; D053613:Janus Kinase 1; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011506:Proteins; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C491411:Socs3 protein, mouse; C491410:Socs3 protein, rat; C494080:Stat1 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; C507906:Jak1 protein, rat; D053613:Janus Kinase 1