Abstract
In addition to the loss of wild-type p53 activity, a high percentage of tumor cells accumulate mutant p53 protein isoforms. Whereas the hallmark of the wild-type p53 is its tumor suppressor activities, tumor-associated mutant p53 proteins acquire novel functions enabling them to promote a large spectrum of cancer phenotypes. During the last years, it became clear that tumor-associated mutant p53 proteins are not only distinct from the wild-type p53, but they also represent a heterogeneous population of proteins with a variety of structure–function features. One of the major mechanisms underlying mutant p53 gain of function is the ability to regulate gene expression. Although a large number of specific target genes were identified, the molecular basis for this regulation is not fully elucidated. This review describes the present knowledge about the transcriptional activities of mutant p53 and the mechanisms that might underlie its target gene specificity.
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Acknowledgements
This research was supported by a Center of Excellence grant from the Flight Attendant Medical Research Institute (FAMRI), EC FP6 Grant LSHC-CT-2004–503576, and Grant R37CA40099 from the National Cancer Institute and Yad Abraham Center for Cancer Diagnosis and Therapy. This publication reflects the authors' views and not necessarily those of the European Community. The EC is not liable for any use that may be made of the information contained herein. VR is the incumbent of the Norman and Helen Asher Professorial Chair Cancer Research at the Weizmann Institute.
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Weisz, L., Oren, M. & Rotter, V. Transcription regulation by mutant p53. Oncogene 26, 2202–2211 (2007). https://doi.org/10.1038/sj.onc.1210294
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