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Molecular Endocrinology, Vol 7, 1275-1283, Copyright © 1993 by Endocrine Society

ARTICLES

Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells

J Leonard, B Peers, T Johnson, K Ferreri, S Lee and MR Montminy
Clayton Foundation Laboratories for Peptide Biology, La Jolla, California 92037.

The endocrine pancreas consists of several differentiated cell types that are distinguished by their selective expression of peptide hormones such as insulin, glucagon, and somatostatin. Although a number of homeobox-type factors have been proposed as key regulators of individual peptide genes in the pancreas, their cellular distribution and relative abundance remain uncharacterized. Also, their overlapping DNA binding specificities have further obscured the regulatory functions these factors perform during development. In this report we characterize a novel homeobox-type somatostatin transactivating factor termed STF-1, which is uniformly expressed in cells of the endocrine pancreas and small intestine. The 283-amino acid STF-1 protein binds to tissue-specific elements within the somatostatin promoter and stimulates somatostatin gene expression both in vivo and in vitro. Remarkably, STF-1 comprises the predominant tissue-specific element- binding activity in nuclear extracts from somatostatin-producing pancreatic islet cells, suggesting that this protein may have a primary role in regulating peptide hormone expression and specifying endocrine cell lineage in the developing gut.


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M. Saji, M. Shong, G. Napolitano, L. A. Palmer, S.-I. Taniguchi, M. Ohmori, M. Ohta, K. Suzuki, S. L. Kirshner, C. Giuliani, et al.
Regulation of Major Histocompatibility Complex Class I Gene Expression in Thyroid Cells. ROLE OF THE cAMP RESPONSE ELEMENT-LIKE SEQUENCE
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 Endocr. Rev.Home page
D. Mitanchez, B. Doiron, R. Chen, and A. Kahn
Glucose-Stimulated Genes and Prospects of Gene Therapy for Type I Diabetes
Endocr. Rev., August 1, 1997; 18(4): 520 - 540.
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 Genes Dev.Home page
M Sander, A Neubuser, J Kalamaras, H C Ee, G R Martin, and M S German
Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development.
Genes & Dev., July 1, 1997; 11(13): 1662 - 1673.
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 Proc. Natl. Acad. Sci. USAHome page
S. Marshak, H. Totary, E. Cerasi, and D. Melloul
Purification of the beta -cell glucose-sensitive factor that transactivates the insulin gene differentially in normal and transformed islet cells
PNAS, December 24, 1996; 93(26): 15057 - 15062.
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B. Laser, P. Meda, I. Constant, and J. Philippe
The caudal-related Homeodomain Protein Cdx-2/3 Regulates Glucagon Gene Expression in Islet Cells
J. Biol. Chem., November 15, 1996; 271(46): 28984 - 28994.
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J. Jensen, P. Serup, C. Karlsen, T. F. Nielsen, and O. D. Madsen
mRNA Profiling of Rat Islet Tumors Reveals Nkx 6.1as a beta -Cell-specific Homeodomain Transcription Factor
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H. Odagiri, J. Wang, and M. S. German
Function of the Human Insulin Promoter in Primary Cultured Islet Cells
J. Biol. Chem., January 26, 1996; 271(4): 1909 - 1915.
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S. Sharma, J. Leonard, S. Lee, H. D. Chapman, E. H. Leiter, and M. R. Montminy
Pancreatic Islet Expression of the Homeobox Factor STF-1 Relies on an E-box Motif That Binds USF
J. Biol. Chem., January 26, 1996; 271(4): 2294 - 2299.
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 DevelopmentHome page
M. Offield, T. Jetton, P. Labosky, M Ray, R. Stein, M. Magnuson, B. Hogan, and C. Wright
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
Development, January 3, 1996; 122(3): 983 - 995.
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P. Briata, R. Van De Werken, I. Airoldi, C. Ilengo, E. Di Blas, E. Boncinelli, and G. Corte
Transcriptional Repression by the Human Homeobox Protein EVX1 in Transfected Mammalian Cells
J. Biol. Chem., November 17, 1995; 270(46): 27695 - 27701.
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M. Wang and D. J. Drucker
The LIM Domain Homeobox Gene isl-1 Is a Positive Regulator of Islet Cell-specific Proglucagon Gene Transcription
J. Biol. Chem., May 26, 1995; 270(21): 12646 - 12652.
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D. C. Chung, S. J. Brand, and L. G. Tillotson
Mutually Exclusive Interactions between Factors Binding to Adjacent Sp1 and AT-rich Elements Regulate Gastrin Gene Transcription in Insulinoma Cells
J. Biol. Chem., April 14, 1995; 270(15): 8829 - 8836.
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C. Morel, M. Cordier-Bussat, and J. Philippe
The Upstream Promoter Element of the Glucagon Gene, G1, Confers Pancreatic Alpha Cell-specific Expression
J. Biol. Chem., February 17, 1995; 270(7): 3046 - 3055.
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Y Guz, M. Montminy, R Stein, J Leonard, L. Gamer, C. Wright, and G Teitelman
Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny
Development, January 1, 1995; 121(1): 11 - 18.
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P. T. Schwartz, B. Perez-Villamil, A. Rivera, R. Moratalla, and M. Vallejo
Pancreatic Homeodomain Transcription Factor IDX1/IPF1 Expressed in Developing Brain Regulates Somatostatin Gene Transcription in Embryonic Neural Cells
J. Biol. Chem., June 16, 2000; 275(25): 19106 - 19114.
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L. Wagner, O. Oliyarnyk, W. Gartner, P. Nowotny, M. Groeger, K. Kaserer, W. Waldhausl, and M. S. Pasternack
Cloning and Expression of Secretagogin, a Novel Neuroendocrine- and Pancreatic Islet of Langerhans-specific Ca2+-binding Protein
J. Biol. Chem., August 4, 2000; 275(32): 24740 - 24751.
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M. R. Dusing, E. A. Florence, and D. A. Wiginton
PDX-1 Is Required for Activation in Vivo from a Duodenum-specific Enhancer
J. Biol. Chem., April 20, 2001; 276(17): 14434 - 14442.
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H. Kaneto, G. Xu, K.-H. Song, K. Suzuma, S. Bonner-Weir, A. Sharma, and G. C. Weir
Activation of the Hexosamine Pathway Leads to Deterioration of Pancreatic beta -Cell Function through the Induction of Oxidative Stress
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 Proc. Natl. Acad. Sci. USAHome page
S. Dutta, M. Gannon, B. Peers, C. Wright, S. Bonner-Weir, and M. Montminy
PDX:PBX complexes are required for normal proliferation of pancreatic cells during development
PNAS, January 30, 2001; 98(3): 1065 - 1070.
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