标题：Specificity in transforming growth factor β-induced transcription of the plasminogen activator inhibitor-1 gene: Interactions of promoter DNA, transcription factor μE3, and Smad proteins
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：23
页码：13130-13135
DOI：10.1073/pnas.96.23.13130
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Transforming growth factor {beta} (TGF-{beta}) regulates a broad range of biological processes, including cell growth, development, differentiation, and immunity. TGF-{beta} signals through its cell surface receptor serine kinases that phosphorylate Smad2 or Smad3 proteins. Because Smad3 and its partner Smad4 bind to only 4-bp Smad binding elements (SBEs) in DNA, a central question is how specificity of TGF-{beta}-induced transcription is achieved. We show that Smad3 selectively binds to two of the three SBEs in PE2.1, a TGF-{beta}-inducible fragment of the plasminogen activator inhibitor-1 promoter, to mediate TGF-{beta}-induced transcription; moreover, a precise 3-bp spacer between one SBE and the E-box, a binding site for transcription factor {micro}E3 (TFE3), is essential for TGF-{beta}-induced transcription. Whereas an isolated Smad3 MH1 domain binds to TFE3, TGF-{beta} receptor-mediated phosphorylation of full-length Smad3 enhances its binding to TFE3. Together, these studies elucidate an important mechanism for specificity in TGF-{beta}-induced transcription of the plasminogen activator inhibitor-1 gene.
