Fragments of neurofibromin (NF1) and method to reverse activated

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence

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530350, 435194, 435 691, C07K 1400, C07K 14435, C07K 1447, C12N 1512

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active

055809553

ABSTRACT:
This invention provides for a mechanism to reverse the activated Ras induced malignant transformation of mammalian cells by use of certain peptides. Specifically, the anti-oncogenic protein fragments of the Neurofibromatosis type 1 protein (NF1) were found to reverse, inhibit, or otherwise interfere with the malignant transformation of V-HaRas induced transformed cells. The invention further identifies several specific fragments of the NF1 protein which are capable of reversing activated Ras induced transformation, including the NF338, NF91, NF78 and NF56 protein fragments. The invention also provides for nucleic acid molecules, cell lines, and expression vectors associated with the NF1 fragments, in addition to protein complexes of the NF1 and Ras proteins. A method for screening molecules which are capable of reversing activated Ras induced transformation is also disclosed herein. Further described herein are pharmaceutical compositions containing the NF1 protein fragment or the nucleic acid molecules coding for the protein fragments. Methods for treating conditions characterized by activated Ras induced malignant transformation with the compositions.

REFERENCES:
patent: 5227292 (1993-07-01), White
Marchuk et al., "cDNA Cloning of the Type 1 Neurofibromatosis Gene: Complete Sequence of the NF1 Gene Product", Genomics 11: 931-940 (1991).
Japanese Biochemical Society Meeting (Oct. 1993) Maruta, H. et al.
Nur-E-Kamal et al., J. Biological Chemistry, vol. 268, No. 8, (Oct. 1993).
Martin, G. A. et al. Cell 63:843-849 (1990).
Wiesmuller, L. et al. J. Biol. Chem. 267:10207-10210 (1992).
Cawthon, R. M. et al. Cell 62:193-201 (1990).

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