From Engaging DNA to Target Gene Regulation
Nucleic Acids Research, 2020 1 doi: 10.1093/nar/gkaa666 SURVEY AND SUMMARY Tumor suppressor p53: from engaging DNA to target Downloaded from https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkaa666/5892750 by University at Albany user on 14 August 2020 gene regulation Morgan A. Sammons 1,*,†, Thuy-Ai T. Nguyen 2,*,†, Simon S. McDade 3,*,† and Martin Fischer 4,*,† 1Department of Biological Sciences and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA, 2Genome Integrity & Structural Biology Laboratory and Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences/National Institutes of Health, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA, 3Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK and 4Computational Biology Group, Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany Received May 24, 2020; Revised July 24, 2020; Editorial Decision July 28, 2020; Accepted July 30, 2020 ABSTRACT INTRODUCTION The p53 transcription factor confers its potent tumor The TP53 gene encoding the tumor suppressor p53 is the suppressor functions primarily through the regula- most frequently mutated gene in human cancers (1,2). p53 tion of a large network of target genes. The recent ex- is also deactivated or repressed in a large proportion of tu- plosion of next generation sequencing protocols has mors containing wild-type p53 through diverse mechanisms enabled the study of the p53 gene regulatory network including aberrant degradation, deregulation of activators, effectors, or repressors such that most, if not all, cancers cir- (GRN) and underlying mechanisms at an unprece- cumvent the p53 signaling pathway.
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