The Tail That Wags the Dog: How the Disordered C-Terminal Domain Controls the Transcriptional Activities of the p53 Tumor-Suppressor Protein Oleg Laptenko,

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The Tail That Wags the Dog: How the Disordered C-Terminal Domain Controls the Transcriptional Activities of the p53 Tumor-Suppressor Protein Oleg Laptenko, David R. Tong, James Manfredi, Carol Prives Trends in Biochemical Sciences Volume 41, Issue 12, Pages 1022-1034 (December 2016) DOI: 10.1016/j.tibs.2016.08.011 Copyright © 2016 Terms and Conditions

Figure 1 Domain Organization of p53 and Functions of the C-Terminal Domain. The upper portion shows p53 domains boundaries (corresponds to human p53 major isoform α) together with their general structural classification. Abbreviations: CTD, C-terminal domain; DBD, DNA-binding domain; NTD, N-terminal transactivation domain; OD, oligomerization domain; PR, proline-rich domain. Solved structures of the DBD (PDB: 2AC0) and OD (PDB: 1PES) shown above the schematic p53 representation. The bottom portion of the figure shows the amino acid sequence of the human p53 CTD. Positively charged residues within this domain are in bold blue font. The functions of the CTD discussed in this review are listed. Trends in Biochemical Sciences 2016 41, 1022-1034DOI: (10.1016/j.tibs.2016.08.011) Copyright © 2016 Terms and Conditions

Figure 2 Alignment of the p53 C-Terminal Domains from 32 Species: 19 Mammals, Four Reptiles, and Nine Fishes. All p53 sequences are from www.ncbi.nlm.nih.gov/gene. The alignment was performed by Clustal W using MegAlign 5.03 software by DNASTAR Inc. The conserved amino acids are shaded. Trends in Biochemical Sciences 2016 41, 1022-1034DOI: (10.1016/j.tibs.2016.08.011) Copyright © 2016 Terms and Conditions

Figure 3 Post-Translational Modifications (PTMs) within the C-Terminal Domain (CTD) of p53. (A) PTM sites within the CTD according to a comprehensive MS analysis [72]. Only the most-abundant modifications detected in [72] are indicated. (Below) Alignment of the p53 CTDs derived from the organisms most commonly used in cancer research and cancer models. (B) Representative examples of various structural shapes of the CTD (shown in dark blue) induced by intermolecular interactions with different cofactors (from left to right): S100B(ββ) (PDB: 1DT7), CBP bromodomain (PDB: 1JSP), and TTD 53BP1 (PDB: 2MWP and 4X34). Trends in Biochemical Sciences 2016 41, 1022-1034DOI: (10.1016/j.tibs.2016.08.011) Copyright © 2016 Terms and Conditions