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Structure of p73 DNA-binding domain tetramer modulates p73 transactivation.

Ethayathulla AS, Tse PW, Monti P, Nguyen S, Inga A, Fronza G, Viadiu H
Proc Natl Acad Sci U S A 109 6066-71 (2012)
Related entries: 3vd0, 3vd2

Cited: 35 times
EuropePMC logo PMID: 22474346

Abstract

The transcription factor p73 triggers developmental pathways and overlaps stress-induced p53 transcriptional pathways. How p53-family response elements determine and regulate transcriptional specificity remains an unsolved problem. In this work, we have determined the first crystal structures of p73 DNA-binding domain tetramer bound to response elements with spacers of different length. The structure and function of the adaptable tetramer are determined by the distance between two half-sites. The structures with zero and one base-pair spacers show compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a two base-pair spacer results in DNA unwinding and a smaller tetramerization interface, whereas a four base-pair spacer hinders tetramerization. Functionally, p73 is more sensitive to spacer length than p53, with one base-pair spacer reducing 90% of transactivation activity and longer spacers reducing transactivation to basal levels. Our results establish the quaternary structure of the p73 DNA-binding domain required as a scaffold to promote transactivation.

Articles - 3vd1 mentioned but not cited (3)

  1. Structure of p73 DNA-binding domain tetramer modulates p73 transactivation. Ethayathulla AS, Tse PW, Monti P, Nguyen S, Inga A, Fronza G, Viadiu H. Proc Natl Acad Sci U S A 109 6066-6071 (2012)
  2. The complexity of protein interactions unravelled from structural disorder. Seoane B, Carbone A. PLoS Comput Biol 17 e1008546 (2021)
  3. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)


Reviews citing this publication (7)

  1. How the TP53 family proteins TP63 and TP73 contribute to tumorigenesis: regulators and effectors. Candi E, Agostini M, Melino G, Bernassola F. Hum Mutat 35 702-714 (2014)
  2. Structure and apoptotic function of p73. Yoon MK, Ha JH, Lee MS, Chi SW. BMB Rep 48 81-90 (2015)
  3. New insights into Hoogsteen base pairs in DNA duplexes from a structure-based survey. Zhou H, Hintze BJ, Kimsey IJ, Sathyamoorthy B, Yang S, Richardson JS, Al-Hashimi HM. Nucleic Acids Res 43 3420-3433 (2015)
  4. Roles of p53 Family Structure and Function in Non-Canonical Response Element Binding and Activation. Cai BH, Chao CF, Huang HC, Lee HY, Kannagi R, Chen JY. Int J Mol Sci 20 E3681 (2019)
  5. Structural diversity of p63 and p73 isoforms. Osterburg C, Dötsch V. Cell Death Differ 29 921-937 (2022)
  6. Increasing occurrences and functional roles for high energy purine-pyrimidine base-pairs in nucleic acids. Kimsey I, Al-Hashimi HM. Curr Opin Struct Biol 24 72-80 (2014)
  7. Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy. Timofeev O, Stiewe T. Cancers (Basel) 13 2422 (2021)

Articles citing this publication (25)

  1. Functional interplay between MDM2, p63/p73 and mutant p53. Stindt MH, Muller PA, Ludwig RL, Kehrloesser S, Dötsch V, Vousden KH. Oncogene 34 4300-4310 (2015)
  2. Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion. Chen Y, Zhang X, Dantas Machado AC, Ding Y, Chen Z, Qin PZ, Rohs R, Chen L. Nucleic Acids Res 41 8368-8376 (2013)
  3. Identification of new p53 target microRNAs by bioinformatics and functional analysis. Bisio A, De Sanctis V, Del Vescovo V, Denti MA, Jegga AG, Inga A, Ciribilli Y. BMC Cancer 13 552 (2013)
  4. Role of chromatin and transcriptional co-regulators in mediating p63-genome interactions in keratinocytes. Sethi I, Sinha S, Buck MJ. BMC Genomics 15 1042 (2014)
  5. ERβ decreases the invasiveness of triple-negative breast cancer cells by regulating mutant p53 oncogenic function. Bado I, Nikolos F, Rajapaksa G, Gustafsson JÅ, Thomas C. Oncotarget 7 13599-13611 (2016)
  6. P53 family members modulate the expression of PRODH, but not PRODH2, via intronic p53 response elements. Raimondi I, Ciribilli Y, Monti P, Bisio A, Pollegioni L, Fronza G, Inga A, Campomenosi P. PLoS One 8 e69152 (2013)
  7. Defining TP53 pioneering capabilities with competitive nucleosome binding assays. Yu X, Buck MJ. Genome Res 29 107-115 (2019)
  8. Reversal of the DNA-binding-induced loop L1 conformational switch in an engineered human p53 protein. Emamzadah S, Tropia L, Vincenti I, Falquet B, Halazonetis TD. J Mol Biol 426 936-944 (2014)
  9. TP53 mutants in the tower of babel of cancer progression. Bisio A, Ciribilli Y, Fronza G, Inga A, Monti P. Hum Mutat 35 689-701 (2014)
  10. Transactivation specificity is conserved among p53 family proteins and depends on a response element sequence code. Ciribilli Y, Monti P, Bisio A, Nguyen HT, Ethayathulla AS, Ramos A, Foggetti G, Menichini P, Menendez D, Resnick MA, Viadiu H, Fronza G, Inga A. Nucleic Acids Res 41 8637-8653 (2013)
  11. YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues. Liu M, Zhao S, Lin Q, Wang XP. Mol Cell Biol 35 1449-1461 (2015)
  12. Molecular dynamics of the full-length p53 monomer. Chillemi G, Davidovich P, D'Abramo M, Mametnabiev T, Garabadzhiu AV, Desideri A, Melino G. Cell Cycle 12 3098-3108 (2013)
  13. Modulation of Hoogsteen dynamics on DNA recognition. Xu Y, McSally J, Andricioaei I, Al-Hashimi HM. Nat Commun 9 1473 (2018)
  14. Transcription factor p73 regulates Th1 differentiation. Ren M, Kazemian M, Zheng M, He J, Li P, Oh J, Liao W, Li J, Rajaseelan J, Kelsall BL, Peltz G, Leonard WJ. Nat Commun 11 1475 (2020)
  15. ∆N-P63α and TA-P63α exhibit intrinsic differences in transactivation specificities that depend on distinct features of DNA target sites. Monti P, Ciribilli Y, Bisio A, Foggetti G, Raimondi I, Campomenosi P, Menichini P, Fronza G, Inga A. Oncotarget 5 2116-2130 (2014)
  16. Structure and stability insights into tumour suppressor p53 evolutionary related proteins. Pagano B, Jama A, Martinez P, Akanho E, Bui TT, Drake AF, Fraternali F, Nikolova PV. PLoS One 8 e76014 (2013)
  17. Crystal structures of the DNA-binding domain tetramer of the p53 tumor suppressor family member p73 bound to different full-site response elements. Ethayathulla AS, Nguyen HT, Viadiu H. J Biol Chem 288 4744-4754 (2013)
  18. EEC- and ADULT-associated TP63 mutations exhibit functional heterogeneity toward P63 responsive sequences. Monti P, Russo D, Bocciardi R, Foggetti G, Menichini P, Divizia MT, Lerone M, Graziano C, Wischmeijer A, Viadiu H, Ravazzolo R, Inga A, Fronza G. Hum Mutat 34 894-904 (2013)
  19. Distinct mechanisms control genome recognition by p53 at its target genes linked to different cell fates. Farkas M, Hashimoto H, Bi Y, Davuluri RV, Resnick-Silverman L, Manfredi JJ, Debler EW, McMahon SB. Nat Commun 12 484 (2021)
  20. MCL1 binds and negatively regulates the transcriptional function of tumor suppressor p73. Widden H, Kaczmarczyk A, Subedi A, Whitaker RH, Placzek WJ. Cell Death Dis 11 946 (2020)
  21. Characterizing Watson-Crick versus Hoogsteen Base Pairing in a DNA-Protein Complex Using Nuclear Magnetic Resonance and Site-Specifically 13C- and 15N-Labeled DNA. Zhou H, Sathyamoorthy B, Stelling A, Xu Y, Xue Y, Pigli YZ, Case DA, Rice PA, Al-Hashimi HM. Biochemistry 58 1963-1974 (2019)
  22. Purifying selection in deeply conserved human enhancers is more consistent than in coding sequences. De Silva DR, Nichols R, Elgar G. PLoS One 9 e103357 (2014)
  23. p73, like its p53 homolog, shows preference for inverted repeats forming cruciforms. Čechová J, Coufal J, Jagelská EB, Fojta M, Brázda V. PLoS One 13 e0195835 (2018)
  24. Pirh2, an E3 ligase, regulates the AIP4-p73 regulatory pathway by modulating AIP4 expression and ubiquitination. Abou Zeinab R, Wu HH, Abuetabh Y, Leng S, Sergi C, Eisenstat DD, Leng RP. Carcinogenesis 42 650-662 (2021)
  25. Disease-related p63 DBD mutations impair DNA binding by distinct mechanisms and varying degree. Osterburg C, Ferniani M, Antonini D, Frombach AS, D'Auria L, Osterburg S, Lotz R, Löhr F, Kehrloesser S, Zhou H, Missero C, Dötsch V. Cell Death Dis 14 274 (2023)


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