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2001 | 48 | 1 | 221-226
Article title

A novel isoform of human lymphoid enhancer-binding factor-1 (LEF-1) gene transcript encodes a protein devoid of HMG domain and nuclear localization signal.

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EN
Abstracts
EN
Lymphoid enhancer-binding factor-1 (LEF-1), a member of the high mobility group (HMG) family of proteins, regulates expression of T-cell receptor-α gene and is one of the key regulatory molecules in the epithelial-mesenchymal interactions during embryonic development. Among others, LEF-1 regulates expression of cytokeratin genes involved in formation of hair follicles and the gene encoding the cell-adhesion molecule E-cadherin. Transcription factor LEF-1, which acts as a dimer, binds β-catenin and is involved in signal transduction by the wnt pathway. We have cloned and sequenced a novel isoform of human LEF-1 gene transcript. This isoform encodes a truncated protein devoid of HMG domain and nuclear localization signal but retaining β-catenin binding domain. This isoform might either act in a dominant-negative manner by interfering with native LEF-1, or might bind β-catenin in the cytosol, which would result in attenuation of the signals transmitted by theLEF-b-catenin pathway.
Publisher

Year
Volume
48
Issue
1
Pages
221-226
Physical description
Dates
published
2001
received
2001-01-29
revised
2001-02-1
Contributors
  • Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland
  • Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland
  • Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland
References
  • 1. Giese, K. & Grosschedl, R. (1993) LEF-1 contains an activation domain that stimulates transcription only in a specific context of factor-binding sites. EMBO J. 12, 4667-4676.
  • 2. Travis, A., Amsterdam, A., Belanger, C. & Grosschedl, R. (1991) LEF-1. A gene encoding a lymphoid-specific protein with an HMG domain regulates T-cell receptor alpha enhancer function. Genes Dev. 5, 880-894.
  • 3. Love, J.J., Li, X., Case, D.A., Giese, K., Grosschedl, R. & Wright, P.E. (1995) Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature 376, 791-795.
  • 4. Genderen van, C., Okamura, R.M., Farinas, I., Quo, R.G., Parslow, T.G., Bruhn, L. & Grosschedl, R. (1994) Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1 deficient mice. Genes Dev. 8, 2691-2703.
  • 5. Behrens, J., von Kries, J.P., Kuehl, M., Bruhn, L., Wedlich, D., Grosschedl, R. & Birchmeier, W. (1996) Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 382, 638-642.
  • 6. Zhou, P., Byrne, C., Jacobs, J. & Fuchs, E. (1995) Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. Genes Dev. 9, 570-583.
  • 7. Kratochwil, K., Dull, M., Farinas, I., Galceran, J. & Grosschedl, R. (1996) Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development. Genes Dev. 10, 1382-1394.
  • 8. Kere, J., Srivastava, A.K., Montonen, O., Zonana, J., Thomas, N., Ferguson, B., Munoz, F., Morgan, D., Clarke, A., Baybayan, P., Chen, E.Y., Ezer, S., Saarialho-Kere, U., de la Chapelle, A. & Schlessinger, D. (1996) X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caued by mutation in a novel transmembrane protein. Nat. Genet. 13, 409-416.
  • 9. Zonana, J., Gault, J., Davies, K.J.P., Jones, M., Browne, D., Litt, J., Brockdorff, N., Rastan, S., Clarke, A. & Thomas, N.S.T. (1993) Detection of a molecular deletion at the DXS732 locus in a patient with X-linked hypohidrotic ectodermal dysplasia (EDA) with the identification of a unique junctional fragment. Am. J. Hum. Genet. 52, 78-84.
  • 10. Waterman, M.L., Fischer, W.H. & Jones, K.A. (1991) A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer. Genes Dev. 5, 656-669.
  • 11. Kobielak, K., Kobielak, A. & Trzeciak, W.H. (1999) Cloning of the lymphoid enhancer binding factor-1 (Lef-1) cDNA from rat kidney: Homology to the mouse sequence. Acta Biochim. Polon. 46, 885-888.
  • 12. Hovanes, K., Li, W.H. & Waterman, M.L. (2000) The human LEF-1 contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing. Nucleic Acids Res. 29, 1994-2003.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv48i1p221kz
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