Tumour Suppressor Protein

Abstract

We describe a polypeptide which binds and modulates the activity of a tumour suppressor polypeptide, for example p53; a nucleic acid molecule encoding said protein and screening methods which modulate the binding activity of said polypeptide for its target polypeptide(s).

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional application of U.S. patent application Ser. No. 10 / 582,316 which is the U.S. National Stage of International Application No. PCT / GB2004 / 003492, filed Aug. 13, 2004 (published in English under PCT Article 21(2)), which in turn claims the benefit of Great Britain Application No. 0328690.3, filed Dec. 10, 2003 and U.S. Provisional Application No. 60 / 554,990, filed Mar. 19, 2004. The disclosure of each priority application is incorporated herein by reference in its entirety.FIELD[0002]The invention relates to a protein that binds and modulates the activity of a tumour suppressor protein, for example p53; a nucleic acid molecule encoding said protein and screening methods which modulate the binding activity of said polypeptide for its target polypeptide.BACKGROUND[0003]Tumour suppressor genes encode proteins which function to inhibit cell growth or division and are therefore important with respect to maintainin...

AI Technical Summary

Benefits of technology

[0099]It will be apparent to one skilled in the art that modification to the amino acid sequence of peptides agents could enhance the binding and / or stability of the peptide with respect to its target sequence. In addition, modification of the peptide may also increase the in vivo stability of the peptide thereby reducing the effective amount of peptide necessary to inhibit p53 binding of iASPP. This would advantageously reduce undesirable side effects which may result in vivo. Modifications include, by example and not by way of limitation, acetylation and amidation. Alternatively or preferably, said modification includes the use of modified amino acids in the production of recombinant or synthetic forms of peptides. It will be apparent to one skilled in the art that modified amino acids include, by way of example and not by way of limitation, 4-hydroxyproline, 5-hydroxylysine, N6-acetyllysine, N6-methyllysine, N6,N6-dimethyllysine, N6,N6,N6-trimethyllysine, cyclohexyalanine, D-amino acids, ornithine. Other modifications include amino acids with a C2, C3 or C4 alkyl R group optionally substituted by 1, 2 or 3 substituents selected from halo (eg F, Br, I), hydroxy or C1-C4 alkoxy. Modifications also include, by example and not by way of limitation, acetylation and amidation.

Problems solved by technology

Mutations in tumour suppressor genes result in abnormal cell-cycle progression whereby the normal cell-cycle check points which arrest the cell-cycle, when, for example, DNA is damaged, are ignored and damaged cells divide uncontrollably.

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