Mutant human hedgehog gene

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

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4353201, 530350, 536 231, 935 22, C12P 2106, C12N 1500, C07K 100, C07H 2102

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057598118

ABSTRACT:
A mutation in the human sonic hedgehog gene is associated with tumorigenesis. A variety of human tumors, including basal cell carcinomas, breast carcinomas, medulloblastomas, etc., have a somatic mutation that a mutation at position 114. Such mutated genes and fragments thereof, encoded protein, and antibodies specific for the mutated protein are useful in characterizing the phenotype of associated tumors. The mutant protein is useful in drug screening for compositions that antagonize or otherwise modulate HH activity or expression. The encoded protein is also used as a therapeutic, to modulate cell proliferation and differentiation, and treatment of pathological conditions associated with decreased hedgehog signaling.

REFERENCES:
Oro et al. (1997) Basal cell carcinoma in mice overexpressing sonic hedgehog. Science 276: 817-821, May 2, 1997.
Fan et al. (1997) Induction to basal cell carcinoma features in transgenic human skin expressing sonic hedgehog. Nature Medicine 3 (7): 788-792, Jun. 1997.
Rudinger (1976) Characteristics of the amino as components of a peptide hormone sequence. In:Peptide Hormeones, Ed. J. A. Parsons, University park Press, Baltimore, MD, pp. 1-7, Jan. 1976.
Gailani et al. (1996) The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nature Genetics 14: 78-81, Sep. 14, 1998.
Roessler et al. (1996) Mutations in the human Sonic hedgehog gene cause holoprosencephaly. Nature Genetics 14: 357-360, Nov. 14, 1996.
Marigo et al. (1995) Cloning, expression and chromosomal location of SHH and IHH: Two human homologues of the Drosophila segment polarity gene hedgehog. Genomics 28: 44-51 Jul. 1, 1995.
Hahn et al. (1996) Mutations of the human homolog of Drosphila patched in the neviod basal cell carcinoma syndrome. Cell 85: 841-851, Jun. 14, 1996.
Hammerschmidt et al. (1997) The World according to hedgehog. Trends in Genetics 13(1): 14-21, Jan. 1, 1997.
Stone et al. (196) The tumor-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature 384: 129-134, Nov. 14, 1996.
Ogura et al. (1996) Evidence that Shh cooperates with a retinoic acid inducible co-factor to establish ZPA-like activity. Development 122: 537-542, Feb. 1996.

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