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Human involucrin (hINV) is a cornified envelope precursor that
is specifically expressed in the suprabasal epidermal layers. We
previously demonstrated that 2500 base pairs of the hINV gene upstream
regulatory region confers differentiation appropriate regulation in
transgenic mice. An analysis of the hINV gene sequence upstream of the
transcription start site reveals five potential AP1 binding sites
(AP1-1 to 5). Using reporter gene constructs in human
keratinocytes, we show that the most distal (AP1-5) and most
proximal (AP1-1) AP1 sites are essential for high level
transcriptional activity. Simultaneous mutation of these sites reduces
transcription by 80%. Gel supershift experiments indicate the
interaction of these sites with Fra-1, junB, and
junD. Involucrin mRNA levels increase 10-fold and promoter
activity 5-11-fold when differentiation is induced by phorbol
ester. Functional studies implicate AP1-1 and AP1-5 in
mediating the phorbol ester-dependent increase in promoter activity. No
involucrin promoter activity or involucrin mRNA was detected in 3T3
fibroblasts. We conclude that (i) two AP1 sites in the hINV promoter
are important elements required for keratinocyte-specific expression,
(ii) these AP1-1 sites mediate the phorbol ester-dependent
increase in promoter activity, and (iii) Fra-1, junB,
and junD may be important regulators of hINV expression in
epidermis.
Volume 270,
Number 21,
Issue of May 26, pp. 12614-12622, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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E. Lengyel, H. Wang, E. Stepp, J. Juarez, Y. Wang, W. Doe, C. M. Pfarr, and D. Boyd Requirement of an Upstream AP-1 Motif for the Constitutive and Phorbol Ester-inducible Expression of the Urokinase-type Plasminogen Activator Receptor Gene J. Biol. Chem., September 20, 1996; 271(38): 23176 - 23184. [Abstract] [Full Text] [PDF]
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D. C. Ng, S. Shafaee, D. Lee, and D. D. Bikle Requirement of an AP-1 Site in the Calcium Response Region of the Involucrin Promoter J. Biol. Chem., July 28, 2000; 275(31): 24080 - 24088. [Abstract] [Full Text] [PDF]
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S. R. Dashti, T. Efimova, and R. L. Eckert MEK6 Regulates Human Involucrin Gene Expression via a p38alpha - and p38delta -dependent Mechanism J. Biol. Chem., July 13, 2001; 276(29): 27214 - 27220. [Abstract] [Full Text] [PDF]
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S. Balasubramanian, T. Efimova, and R. L. Eckert Green Tea Polyphenol Stimulates a Ras, MEKK1, MEK3, and p38 Cascade to Increase Activator Protein 1 Factor-dependent Involucrin Gene Expression in Normal Human Keratinocytes J. Biol. Chem., January 11, 2002; 277(3): 1828 - 1836. [Abstract] [Full Text] [PDF]
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