Divergent regulation of the growth-promoting gene IEX-1 by the p53 tumor suppressor and Sp1

Hee Jeong Im, Mark R. Pittelkow, Rajiv Kumar

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

IEX-1, a recently discovered early response gene, regulates cell growth and apoptosis. IEX-1 gene expression is regulated by a variety of factors such as x-irradiation, ultraviolet radiation, steroids, growth factors, and inflammatory stimuli. By systematic examination of the IEX-1 promoter, we show that IEX-1 gene expression is controlled by multiple conserved gene regulatory elements and that IEX-1 is a downstream target of the p53 tumor suppressor and Sp1. In addition, p300, Sox, nuclear factor-κB, and AP4 appear to be modulators of IEX-1 gene expression to a lesser degree. We found that there is at least one Sp1 element that functions as an activator and contributes to high basal transcriptional levels of the IEX-1 gene. We demonstrate the presence of a p53 response element that represses IEX-1 promoter activity in HaCaT keratinocytes, indicating that Sp1 and p53 have opposite effects on IEX-1 gene expression. We conclude that IEX-1 expression in cells is regulated by the p53 tumor suppressor and Sp1, thus providing a direct mechanism for control of cell proliferation.

Original languageEnglish (US)
Pages (from-to)14612-14621
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number17
DOIs
StatePublished - Apr 26 2002

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Gene expression
Tumors
Genes
Gene Expression
Growth
Neoplasms
Activator Appliances
Cell proliferation
Cell growth
Response Elements
Regulator Genes
Keratinocytes
Ultraviolet radiation
Modulators
Intercellular Signaling Peptides and Proteins
Steroids
Cell Proliferation
Irradiation
Radiation
Apoptosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Divergent regulation of the growth-promoting gene IEX-1 by the p53 tumor suppressor and Sp1. / Im, Hee Jeong; Pittelkow, Mark R.; Kumar, Rajiv.

In: Journal of Biological Chemistry, Vol. 277, No. 17, 26.04.2002, p. 14612-14621.

Research output: Contribution to journalArticle

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