منابع مشابه
Allele-specific p53 mutant reactivation.
Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the National Cancer Institute's anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53(R175) mutant. Mechanistic studies reveal that NSC319726 restores WT structure and...
متن کاملSmall molecule induced reactivation of mutant p53 in cancer cells
The p53 cancer mutant Y220C is an excellent paradigm for rescuing the function of conformationally unstable p53 mutants because it has a unique surface crevice that can be targeted by small-molecule stabilizers. Here, we have identified a compound, PK7088, which is active in vitro: PK7088 bound to the mutant with a dissociation constant of 140 μM and raised its melting temperature, and we have ...
متن کاملReactivation of mutant p53 by a one-hybrid adaptor protein.
The most frequent genetic alteration in cancer is a mutation of p53. In most cases, this leads to a sharp increase of the p53 protein levels but abolishes p53's function as an activator of transcription. To correct this defect, wild-type p53 is being reintroduced into tumor cells through gene therapy vectors, thereby inducing cell death. However, this effect is not necessarily specific for tumo...
متن کاملAllele-specific silencing of mutant p53 attenuates dominant-negative and gain-of-function activities
Many p53 hotspot mutants not only lose the transcriptional activity, but also show dominant-negative (DN) and oncogenic gain-of-function (GOF) activities. Increasing evidence indicates that knockdown of mutant p53 (mutp53) in cancer cells reduces their aggressive properties, suggesting that survival and proliferation of cancer cells are, at least partially, dependent on the presence of mutp53. ...
متن کاملp53 reactivation
Lack of p53 expression or expression of mutant p53 is common in human cancers and is associated with increased tumor growth and resistance to therapies. Significant efforts toward pharmaceutical reactivation of defective p53 by small molecules are therefore underway, targeting the different means that inactivate p53. Indeed, reactivated p53 can lead to tumor destruction. A recent paper in Cance...
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ژورنال
عنوان ژورنال: Cancer Cell
سال: 2012
ISSN: 1535-6108
DOI: 10.1016/j.ccr.2012.03.042