25 Years of P53 Research by Pierre Hainaut, Klas G. Wiman

By Pierre Hainaut, Klas G. Wiman

P53 has emerged as a key tumor suppressor and demanding aim for novel melanoma treatment. This booklet, written through world-leading p53 researchers together with a lot of those that have formed the sector during the last 25 years, presents special insights into the development of the sphere and the customers for higher melanoma prognosis and remedy sooner or later.

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Mutant Rescue Restoring the DNA binding function of p53 mutant proteins which are highly expressed in tumors has long been a prominent goal in the field (reviewed in Bullock & Fersht, 2001). , 1994). , 1999). Many if not all of these so-called “hot-spot” mutations result in less thermodynamically stable proteins. , 1996b). , 2004). 2. Regulation of p53 DNA Binding 35 These and other data led to the design of large-scale screens for compounds that could increase p53 mutant sequence-specific DNA binding.

Dynamics of the p53-Mdm2 feedback loop in individual cells. Nature Genetics, 2004. 36: 147-150. A. Cellular oncogenes and multistep carcinogenesis. Science, 1983. 222: 771-778. V. T antigen is bound to a host protein in SV40-transformed cells. Nature, 1979. 278: 261-263. J, Several hydrophobic amino acids in the p53 aminoterminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus E1B 55 kd protein. Genes and Development, 1994. 8: 1235-1246. J. Two critical hydrophobic amino acids in the N-terminal domain of the p53 protein are required for the gain of function phenotypes of human p53 mutants.

99: 14795-14800. Chapter 2 REGULATION OF P53 DNA BINDING Kristine McKinney and Carol Prives Columbia University, Department of Biological Sciences, New York, NY, USA p53 is one of the most frequently mutated genes in human cancers and, as a result, is also one of the most well-studied genes in the history of cancer research. Although many functions have been ascribed to p53 over the years, one of the first activities to be characterized was the ability to bind DNA sequence-specifically through its central domain (reviewed in Vogelstein & Kinzler, 1992).

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