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 similar to1.1 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 (similar to1.1 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. (C) 2003 Elsevier Science (USA). All rights reserved.