Mutant p21Cip1/WAF1 and cell growth control and cell growth control
OwnerMien-Chie Hung, Binhua P. Zhouinventors
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Abstract
Disclosed are methods and compositions regarding separate mutant forms of p21Cip1/WAF1 that are associated with control of cell growth. Substitution of Thr145 with another amino acid, such as Ala, results in failure to be phosphorylated at that site and leads to retention of the polypeptide in the nucleus, resulting in preferentially suppressing growth of transformed cells. Alternatively, substitution of Thr145 with another amino acid, such as Asp, results in cytoplasmic translocation of the polypeptide and results in enhancing cellular survival.
Claims48
A p21Cip1/WAF1 polypeptide comprising an amino acid substitution at Thr145.
A p21Cip1/WAF1 polypeptide comprising a modification which prohibits phosphorylation of the polypeptide under conditions which would result in phosphorylation of an unsubstituted p21Cip1/WAF1 polypeptide, wherein the modification results in accumulation of the polypeptide in a nucleus of a cell under conditions in which the unsubstituted p21Cip1/WAF1 polypeptide would translocate from the nucleus to the cytoplasm of the cell.
A method comprising administering to a cell a p21Cip1/WAF1 polypeptide having an amino acid substitution at Thr145.
A method of obtaining a nuclear-retained polypeptide of p21Cip1/WAF1 which remains in the nucleus following activation of Akt.
A method of identifying a p21Cip1/WAF1 polypeptide which accumulates in the nucleus of a cell following activation by Akt, comprising:
- altering the polypeptide;
- and
- assaying the polypeptide for nuclear accumulation in the cell under conditions wherein an unmodified p21Cip1/WAF1 polypeptide translocalizes from the nucleus to the cytoplasm of the cell.
Dependencies are inferred from the claim text.