NDLI: Regulation of the Human Plasminogen Activator Inhibitor Type 2 Gene COOPERATION OF AN UPSTREAM SILENCER AND TRANSACTIVATOR

Content Provider	Journal of Biological Chemistry (JBC)
Author	Stringer, Brett Udofa, Ekemini A. Antalis, Toni M.
Abstract	Transcriptional up-regulation of the plasminogen activator inhibitor type-2 (PAI-2) gene is a major response to cellular stress. The expression of PAI-2 is induced by a variety of cytokines and growth factors that act in a cell type- and differentiation stage-dependent manner. We previously reported that the human SERPINB2 gene promoter is controlled by three major transcription regulatory domains: an inducible proximal promoter, an upstream silencer (PAUSE-1), and a distal transactivator region between −5100 and −3300, which appears to overcome inhibition mediated by the silencer. The distal transactivator region is inducible by the phorbol ester PMA, a potent activator of the protein kinase C (PKC) pathway that is a powerful inducer of PAI-2 gene expression in monocytes, macrophages, and myelomonocytic cells as well as in epidermal keratinocytes. Here we show that a 21-bp region (−4952/−4932), containing an AP-1 element, is both necessary and sufficient for PMA-induced transactivator activity in PAI-2-expressing U937 cells. This site specifically binds FosB in PAI-2-expressing U937 cells but not in HeLa cells that do not express PAI-2, and overexpression of FosB, c-Fos, or c-Jun in HeLa cells is sufficient to cause derepression of transcription from the SERPINB2 promoter. Although FosB is likely to be involved in transactivator-mediated derepression of PAI-2 transcription in macrophage-like cells, as exemplified by the U937 cell line, c-Jun may be functional in other cell types. These data suggest a model for the transcriptional control of the human PAI-2 gene and further our understanding of the molecular basis for its tissue-specific expression.
Related Links	http://www.jbc.org/content/287/13/10579.abstract
Ending Page	10589
Starting Page	10579
Page Count	11
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	13
Volume Number	287
DOI	10.1074/jbc.M111.318758
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2012-03-23
Access Restriction	Open
Subject Keyword	AP1 transcription factor Fos Gene regulation Phorbol esters Promoters Serpin PAI-2 Derepression Transactivator Molecular Bases of Disease
Alternative Title	Regulation of the Human Plasminogen Activator Inhibitor Type 2 Gene
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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