Gain-of-Function (GOF) Mutant p53 as Actionable Therapeutic Target
نویسندگان
چکیده
منابع مشابه
Mutant p53 gain-of-function in cancer.
In its wild-type form, p53 is a major tumor suppressor whose function is critical for protection against cancer. Many human tumors carry missense mutations in the TP53 gene, encoding p53. Typically, the affected tumor cells accumulate excessive amounts of the mutant p53 protein. Various lines of evidence indicate that, in addition to abrogating the tumor suppressor functions of wild-type p53, t...
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Tumour-derived p53 mutants are thought to have acquired 'gain-of-function' properties that contribute to oncogenicity. We have tested the hypothesis that p53 mutants suppress p53-target gene expression, leading to enhanced cellular growth. Silencing of mutant p53 expression in several human cell lines was found to lead to the upregulation of wild-type p53-target genes such as p21, gadd45, PERP ...
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Cancer is caused by the spatial and temporal accumulation of alterations in the genome of a given cell. This leads to the deregulation of key signalling pathways that play a pivotal role in the control of cell proliferation and cell fate. The p53 tumor suppressor gene is the most frequent target in genetic alterations in human cancers. The primary selective advantage of such mutations is the el...
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p53(R172H/+) mice inherit a p53 mutation found in Li-Fraumeni syndrome and develop metastatic tumors at much higher frequency than p53(+/-) mice. To explore the mutant p53 metastatic phenotype, we used expression arrays to compare primary osteosarcomas from p53(R172H/+) mice with metastasis to osteosarcomas from p53(+/-) mice lacking metastasis. For this study, 213 genes were differentially exp...
متن کاملPhenotype of Mutant p53 Proteins Induction of Gene Amplification as a Gain-of-Function
Gene amplification accompanies tumor progression and is involved in the development of drug resistance. Previously, we reported (A. Albor et al., Cancer Res. 58: 2091–2094, 1998) that mutant p53 proteins conserve the capacity to interact with and activate topoisomerase I, and that this could be a mechanism for induction of genomic instability by mutant p53 proteins. To test this hypothesis, the...
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ژورنال
عنوان ژورنال: Cancers
سال: 2018
ISSN: 2072-6694
DOI: 10.3390/cancers10060188