Characterization of the P300 Taz2-p53 TAD2 Complex and Comparison with the P300 Taz2-p53 TAD1 Complex

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2015 Mar 11

PMID 25753752

Citations 33

Authors

Lisa M Miller Jenkins

Hanqiao Feng

Stewart R Durell

Harichandra D Tagad

Sharlyn J Mazur

Joseph E Tropea

Yawen Bai

Ettore Appella

Affiliations

Soon will be listed here.

Abstract

The p53 tumor suppressor is a critical mediator of the cellular response to stress. The N-terminal transactivation domain of p53 makes protein interactions that promote its function as a transcription factor. Among those cofactors is the histone acetyltransferase p300, which both stabilizes p53 and promotes local chromatin unwinding. Here, we report the nuclear magnetic resonance solution structure of the Taz2 domain of p300 bound to the second transactivation subdomain of p53. In the complex, p53 forms an α-helix between residues 47 and 55 that interacts with the α1-α2-α3 face of Taz2. Mutational analysis indicated several residues in both p53 and Taz2 that are critical for stabilizing the interaction. Finally, further characterization of the complex by isothermal titration calorimetry revealed that complex formation is pH-dependent and releases a bound chloride ion. This study highlights differences in the structures of complexes formed by the two transactivation subdomains of p53 that may be broadly observed and play critical roles in p53 transcriptional activity.

Citing Articles

A foundation model of transcription across human cell types.

Fu X, Mo S, Buendia A, Laurent A, Shao A, Alvarez-Torres M Nature. 2025; 637(8047):965-973.

PMID: 39779852 PMC: 11754112. DOI: 10.1038/s41586-024-08391-z.

High-throughput affinity measurements of direct interactions between activation domains and co-activators.

DelRosso N, Suzuki P, Griffith D, Lotthammer J, Novak B, Kocalar S bioRxiv. 2024; .

PMID: 39229005 PMC: 11370418. DOI: 10.1101/2024.08.19.608698.

Mechanism for controlled assembly of transcriptional condensates by Aire.

Huoh Y, Zhang Q, Torner R, Baca S, Arthanari H, Hur S Nat Immunol. 2024; 25(9):1580-1592.

PMID: 39169234 PMC: 11362013. DOI: 10.1038/s41590-024-01922-w.

Molecular basis of the interactions between the disordered Neh4 and Neh5 domains of Nrf2 and CBP/p300 in oxidative stress response.

Karunatilleke N, Brickenden A, Choy W Protein Sci. 2024; 33(9):e5137.

PMID: 39150085 PMC: 11328122. DOI: 10.1002/pro.5137.

GET: a foundation model of transcription across human cell types.

Fu X, Mo S, Buendia A, Laurent A, Shao A, Alvarez-Torres M bioRxiv. 2024; .

PMID: 39005360 PMC: 11244937. DOI: 10.1101/2023.09.24.559168.

References

Brunger A . Version 1.2 of the Crystallography and NMR system. Nat Protoc. 2007; 2(11):2728-33. DOI: 10.1038/nprot.2007.406. View

Kussie P, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine A . Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science. 1996; 274(5289):948-53. DOI: 10.1126/science.274.5289.948. View

Swanson K, Kang R, Stamenova S, Hicke L, Radhakrishnan I . Solution structure of Vps27 UIM-ubiquitin complex important for endosomal sorting and receptor downregulation. EMBO J. 2003; 22(18):4597-606. PMC: 212737. DOI: 10.1093/emboj/cdg471. View

Momand J, Zambetti G, Olson D, George D, Levine A . The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992; 69(7):1237-45. DOI: 10.1016/0092-8674(92)90644-r. View

Candau R, Scolnick D, Darpino P, YING C, Halazonetis T, Berger S . Two tandem and independent sub-activation domains in the amino terminus of p53 require the adaptor complex for activity. Oncogene. 1997; 15(7):807-16. DOI: 10.1038/sj.onc.1201244. View

Zhu J, Zhang S, Jiang J, Chen X . Definition of the p53 functional domains necessary for inducing apoptosis. J Biol Chem. 2000; 275(51):39927-34. DOI: 10.1074/jbc.M005676200. View

Ogura K, Terasawa H, Inagaki F . An improved double-tuned and isotope-filtered pulse scheme based on a pulsed field gradient and a wide-band inversion shaped pulse. J Biomol NMR. 2010; 8(4):492-8. DOI: 10.1007/BF00228150. View

Wojciak J, Martinez-Yamout M, Dyson H, Wright P . Structural basis for recruitment of CBP/p300 coactivators by STAT1 and STAT2 transactivation domains. EMBO J. 2009; 28(7):948-58. PMC: 2670858. DOI: 10.1038/emboj.2009.30. View

Brady C, Jiang D, Mello S, Johnson T, Jarvis L, Kozak M . Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell. 2011; 145(4):571-83. PMC: 3259909. DOI: 10.1016/j.cell.2011.03.035. View

10.

Osawa M, Tokumitsu H, Swindells M, Kurihara H, Orita M, Shibanuma T . A novel target recognition revealed by calmodulin in complex with Ca2+-calmodulin-dependent kinase kinase. Nat Struct Biol. 1999; 6(9):819-24. DOI: 10.1038/12271. View

11.

He J, Ye J, Cai Y, Riquelme C, Liu J, Liu X . Structure of p300 bound to MEF2 on DNA reveals a mechanism of enhanceosome assembly. Nucleic Acids Res. 2011; 39(10):4464-74. PMC: 3105382. DOI: 10.1093/nar/gkr030. View

12.

Oldfield C, Meng J, Yang J, Yang M, Uversky V, Dunker A . Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners. BMC Genomics. 2008; 9 Suppl 1:S1. PMC: 2386051. DOI: 10.1186/1471-2164-9-S1-S1. View

13.

Popowicz G, Czarna A, Holak T . Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain. Cell Cycle. 2008; 7(15):2441-3. DOI: 10.4161/cc.6365. View

14.

Ferreon J, Martinez-Yamout M, Dyson H, Wright P . Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein. Proc Natl Acad Sci U S A. 2009; 106(32):13260-5. PMC: 2726373. DOI: 10.1073/pnas.0906770106. View

15.

Zhu J, Zhou W, Jiang J, Chen X . Identification of a novel p53 functional domain that is necessary for mediating apoptosis. J Biol Chem. 1998; 273(21):13030-6. DOI: 10.1074/jbc.273.21.13030. View

16.

Barlev N, Liu L, Chehab N, Mansfield K, Harris K, Halazonetis T . Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell. 2002; 8(6):1243-54. DOI: 10.1016/s1097-2765(01)00414-2. View

17.

Bochkareva E, Kaustov L, Ayed A, Yi G, Lu Y, Pineda-Lucena A . Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A. Proc Natl Acad Sci U S A. 2005; 102(43):15412-7. PMC: 1266094. DOI: 10.1073/pnas.0504614102. View

18.

Johnson B, Blevins R . NMR View: A computer program for the visualization and analysis of NMR data. J Biomol NMR. 2012; 4(5):603-14. DOI: 10.1007/BF00404272. View

19.

Lee H, Mok K, Muhandiram R, Park K, Suk J, Kim D . Local structural elements in the mostly unstructured transcriptional activation domain of human p53. J Biol Chem. 2000; 275(38):29426-32. DOI: 10.1074/jbc.M003107200. View

20.

Cornilescu G, Delaglio F, Bax A . Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J Biomol NMR. 1999; 13(3):289-302. DOI: 10.1023/a:1008392405740. View