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(Received for publication, December 29, 1995, and in revised form, April 16, 1996)
From the Departments of A cDNA clone, named gut-enriched
Krüppel-like factor (GKLF), was isolated from an NIH
3T3 library using a probe encoding the zinc finger region of the
immediate-early transcription factor zif/268. The deduced GKLF amino
acid sequence contains three tandem zinc fingers that are related to
members of the Krüppel family of transcription factors. By
indirect immunofluorescence, GKLF is localized to the cell nucleus. In
cultured fibroblasts, GKLF mRNA is found in high levels
in growth-arrested cells and is nearly undetectable in cells that are
in the exponential phase of proliferation. The growth-arresting nature
of GKLF is demonstrated by an inhibition of DNA synthesis in cells
transfected with a GKLF-expressing plasmid construct. In
the mouse, GKLF mRNA is present in select tissues and
is most abundant in the colon, followed by the testis, lung, and small
intestine. In situ hybridization experiments indicate that
GKLF mRNA is enriched in epithelial cells located in
the middle to upper crypt region of the colonic mucosa. Taken together,
these results suggest that GKLF is potentially a negative regulator of
cell growth in tissues such as the gut mucosa, where cell proliferation
is intimately coupled to growth arrest and differentiation.
Volume 271, Number 33,
Issue of August 16, 1996
pp. 20009-20017
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
Medicine and
Biological Chemistry, The Johns Hopkins University School of
Medicine, Baltimore, Maryland 21205 and the ¶ Center for Molecular
Medicine, Institute of Biotechnology, University of Texas Health
Science Center, San Antonio, Texas 78250
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C. Ratineau, M. W. Petry, H. Mutoh, and A. B. Leiter Cyclin D1 Represses the Basic Helix-Loop-Helix Transcription Factor, BETA2/NeuroD J. Biol. Chem., March 8, 2002; 277(11): 8847 - 8853. [Abstract] [Full Text] [PDF]
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 N. Lei and L. L. Heckert Sp1 and Egr1 Regulate Transcription of the Dmrt1 Gene in Sertoli Cells Biol Reprod, March 1, 2002; 66(3): 675 - 684. [Abstract] [Full Text] [PDF]
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J. P. Katz, N. Perreault, B. G. Goldstein, C. S. Lee, P. A. Labosky, V. W. Yang, and K. H. Kaestner The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon Development, January 6, 2002; 129(11): 2619 - 2628. [Abstract] [Full Text] [PDF]
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 W. Zhang, T. Kuncewicz, S. C. Higham, and B. C. Kone Structure, Promoter Analysis, and Chromosomal Localization of the Murine H+/K+-ATPase {alpha}2 Subunit Gene J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2554 - 2564. [Abstract] [Full Text] [PDF]
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K. A. Miller, E. A. Eklund, M. L. Peddinghaus, Z. Cao, N. Fernandes, P. W. Turk, B. Thimmapaya, and S. A. Weitzman Kruppel-like Factor 4 Regulates Laminin alpha 3A Expression in Mammary Epithelial Cells J. Biol. Chem., November 9, 2001; 276(46): 42863 - 42868. [Abstract] [Full Text] [PDF]
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 L. J. Landesberg, R. Ramalingam, K. Lee, T. K. Rosengart, and R. G. Crystal Upregulation of transcription factors in lung in the early phase of postpneumonectomy lung growth Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1138 - L1149. [Abstract] [Full Text] [PDF]
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A. C. Oates, S. J. Pratt, B. Vail, Y.-l. Yan, R. K. Ho, S. L. Johnson, J. H. Postlethwait, and L. I. Zon The zebrafish klf gene family Blood, September 15, 2001; 98(6): 1792 - 1801. [Abstract] [Full Text] [PDF]
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J.-S. Zhang, M. C. Moncrieffe, J. Kaczynski, V. Ellenrieder, F. G. Prendergast, and R. Urrutia A Conserved {alpha}-Helical Motif Mediates the Interaction of Sp1-Like Transcriptional Repressors with the Corepressor mSin3A Mol. Cell. Biol., August 1, 2001; 21(15): 5041 - 5049. [Abstract] [Full Text] [PDF]
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W. Zhang, S. Kadam, B. M. Emerson, and J. J. Bieker Site-Specific Acetylation by p300 or CREB Binding Protein Regulates Erythroid Kruppel-Like Factor Transcriptional Activity via Its Interaction with the SWI-SNF Complex Mol. Cell. Biol., April 1, 2001; 21(7): 2413 - 2422. [Abstract] [Full Text]
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 K. A. Dellow, P. K. Bhavsar, N. J. Brand, and P. J.R. Barton Identification of novel, cardiac-restricted transcription factors binding to a CACC-box within the human cardiac troponin I promoter Cardiovasc Res, April 1, 2001; 50(1): 24 - 33. [Abstract] [Full Text] [PDF]
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L Lei, L Ma, S Nef, T Thai, and L. Parada mKlf7, a potential transcriptional regulator of TrkA nerve growth factor receptor expression in sensory and sympathetic neurons Development, January 4, 2001; 128(7): 1147 - 1158. [Abstract] [PDF]
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K. W. Foster, A. R. Frost, P. McKie-Bell, C.-Y. Lin, J. A. Engler, W. E. Grizzle, and J. M. Ruppert Increase of GKLF Messenger RNA and Protein Expression during Progression of Breast Cancer Cancer Res., November 1, 2000; 60(22): 6488 - 6495. [Abstract] [Full Text]
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 K. Tanimoto, Q. Liu, F. Grosveld, J. Bungert, and J. D. Engel Context-dependent EKLF responsiveness defines the developmental specificity of the human varepsilon -globin gene in erythroid cells of YAC transgenic mice Genes & Dev., November 1, 2000; 14(21): 2778 - 2794. [Abstract] [Full Text]
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S. Uchida, Y. Tanaka, H. Ito, F. Saitoh-Ohara, J. Inazawa, K. K. Yokoyama, S. Sasaki, and F. Marumo Transcriptional Regulation of the CLC-K1 Promoter by myc-Associated Zinc Finger Protein and Kidney-Enriched Kruppel-Like Factor, a Novel Zinc Finger Repressor Mol. Cell. Biol., October 1, 2000; 20(19): 7319 - 7331. [Abstract] [Full Text]
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H. Asano, X. S. Li, and G. Stamatoyannopoulos FKLF-2: a novel Kruppel-like transcriptional factor that activates globin and other erythroid lineage genes Blood, June 1, 2000; 95(11): 3578 - 3584. [Abstract] [Full Text] [PDF]
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D. E. Geiman, H. Ton-That, J. M. Johnson, and V. W. Yang Transactivation and growth suppression by the gut-enriched Kruppel-like factor (Kruppel-like factor 4) are dependent on acidic amino acid residues and protein-protein interaction Nucleic Acids Res., March 1, 2000; 28(5): 1106 - 1113. [Abstract] [Full Text] [PDF]
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K. P. Anderson, S. C. Crable, and J. B. Lingrel The GATA-E box-GATA motif in the EKLF promoter is required for in vivo expression Blood, March 1, 2000; 95(5): 1652 - 1655. [Abstract] [Full Text] [PDF]
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S. Kojima, S. Hayashi, K. Shimokado, Y. Suzuki, J. Shimada, M. P. Crippa, and S. L. Friedman Transcriptional activation of urokinase by the Kruppel-like factor Zf9/COPEB activates latent TGF-beta 1 in vascular endothelial cells Blood, February 15, 2000; 95(4): 1309 - 1316. [Abstract] [Full Text] [PDF]
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K. Kawai-Kowase, M. Kurabayashi, Y. Hoshino, Y. Ohyama, and R. Nagai Transcriptional Activation of the Zinc Finger Transcription Factor BTEB2 Gene by Egr-1 Through Mitogen-Activated Protein Kinase Pathways in Vascular Smooth Muscle Cells Circ. Res., October 29, 1999; 85(9): 787 - 795. [Abstract] [Full Text] [PDF]
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D. Tavares, K. Tully, and P. R. Dobner Sequences Required for Induction of Neurotensin Receptor Gene Expression during Neuronal Differentiation of N1E-115 Neuroblastoma Cells J. Biol. Chem., October 15, 1999; 274(42): 30066 - 30079. [Abstract] [Full Text] [PDF]
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T. Cook, B. Gebelein, M. Belal, K. Mesa, and R. Urrutia Three Conserved Transcriptional Repressor Domains Are a Defining Feature of the TIEG Subfamily of Sp1-like Zinc Finger Proteins J. Biol. Chem., October 8, 1999; 274(41): 29500 - 29504. [Abstract] [Full Text] [PDF]
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M. A. Wani, S. E. Wert, and J. B Lingrel Lung Kruppel-like Factor, a Zinc Finger Transcription Factor, Is Essential for Normal Lung Development J. Biol. Chem., July 23, 1999; 274(30): 21180 - 21185. [Abstract] [Full Text] [PDF]
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N. Watanabe, M. Kurabayashi, Y. Shimomura, K. Kawai-Kowase, Y.-i. Hoshino, I. Manabe, M. Watanabe, M. Aikawa, M. Kuro-o, T. Suzuki, et al. BTEB2, a Kruppel-Like Transcription Factor, Regulates Expression of the SMemb/Nonmuscle Myosin Heavy Chain B (SMemb/NMHC-B) Gene Circ. Res., July 23, 1999; 85(2): 182 - 191. [Abstract] [Full Text] [PDF]
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 K. W. Foster, S. Ren, I. D. Louro, S. M. Lobo-Ruppert, P. McKie-Bell, W. Grizzle, M. R. Hayes, T. R. Broker, L. T. Chow, and J. M. Ruppert Oncogene Expression Cloning by Retroviral Transduction of Adenovirus E1A-immortalized Rat Kidney RK3E Cells: Transformation of a Host with Epithelial Features by c-MYC and the Zinc Finger Protein GKLF Cell Growth Differ., June 1, 1999; 10(6): 423 - 434. [Abstract] [Full Text]
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H. Asano, X. S. Li, and G. Stamatoyannopoulos FKLF, a Novel Kruppel-Like Factor That Activates Human Embryonic and Fetal beta -Like Globin Genes Mol. Cell. Biol., May 1, 1999; 19(5): 3571 - 3579. [Abstract] [Full Text] [PDF]
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P. A. Xu, J. H. Winston, S. K. Datta, and R. E. Kellems Regulation of Forestomach-specific Expression of the Murine Adenosine Deaminase Gene J. Biol. Chem., April 9, 1999; 274(15): 10316 - 10323. [Abstract] [Full Text] [PDF]
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R. Prasad, V. Kumar, R. Kumar, and K. P. Singh Thyroid hormones modulate zinc transport activity of rat intestinal and renal brush-border membrane Am J Physiol Endocrinol Metab, April 1, 1999; 276(4): E774 - E782. [Abstract] [Full Text] [PDF]
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N. Matsumoto, F. Laub, R. Aldabe, W. Zhang, F. Ramirez, T. Yoshida, and M. Terada Cloning the cDNA for a New Human Zinc Finger Protein Defines a Group of Closely Related Kruppel-like Transcription Factors J. Biol. Chem., October 23, 1998; 273(43): 28229 - 28237. [Abstract] [Full Text] [PDF]
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T. Cook, B. Gebelein, K. Mesa, A. Mladek, and R. Urrutia Molecular Cloning and Characterization of TIEG2 Reveals a New Subfamily of Transforming Growth Factor-beta -inducible Sp1-like Zinc Finger-encoding Genes Involved in the Regulation of Cell Growth J. Biol. Chem., October 2, 1998; 273(40): 25929 - 25936. [Abstract] [Full Text] [PDF]
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N. Gillemans, R. Tewari, F. Lindeboom, R. Rottier, T. de Wit, M. Wijgerde, F. Grosveld, and S. Philipsen Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the beta -globin locus control region in vivo Genes & Dev., September 15, 1998; 12(18): 2863 - 2873. [Abstract] [Full Text]
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W. Zhang, J. M. Shields, K. Sogawa, Y. Fujii-Kuriyama, and V. W. Yang The Gut-enriched Kruppel-like Factor Suppresses the Activity of the CYP1A1 Promoter in an Sp1-dependent Fashion J. Biol. Chem., July 10, 1998; 273(28): 17917 - 17925. [Abstract] [Full Text] [PDF]
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