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http://dx.doi.org/10.5483/BMBRep.2015.48.2.255

Structure and apoptotic function of p73  

Yoon, Mi-Kyung (Structural Biology & Nanopore Research Laboratory, Functional Genomics Research Center, KRIBB)
Ha, Ji-Hyang (Structural Biology & Nanopore Research Laboratory, Functional Genomics Research Center, KRIBB)
Lee, Min-Sung (Structural Biology & Nanopore Research Laboratory, Functional Genomics Research Center, KRIBB)
Chi, Seung-Wook (Structural Biology & Nanopore Research Laboratory, Functional Genomics Research Center, KRIBB)
Publication Information
BMB Reports / v.48, no.2, 2015 , pp. 81-90 More about this Journal
Abstract
p73 is a structural and functional homologue of the p53 tumor suppressor protein. Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity. In addition, p73 has unique roles in neuronal development and differentiation. The importance of p73-induced apoptosis lies in its capability to substitute the pro-apoptotic activity of p53 in various human cancer cells in which p53 is mutated or inactive. Despite the great importance of p73-induced apoptosis in cancer therapy, little is known about the molecular basis of p73-induced apoptosis. In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.
Keywords
Apoptosis; Cancer therapy; p53 protein family; p73; Structure;
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1 Dötsch V, Bernassola F, Coutandin D, Candi E and Melino G (2010) p63 and p73, the ancestors of p53. Cold Spring Harb Perspect Biol 2, a004887   DOI
2 Cutruzzola F, Avigliano L and Candi E (2014) p73 keeps metabolic control in balance. Cell Cycle 13, 179-180   DOI   ScienceOn
3 Inoue S, Tomasini R, Rufini A et al (2014) TAp73 is required for spermatogenesis and the maintenance of male fertility. Proc Natl Acad Sci U S A 111, 1843-1848   DOI   ScienceOn
4 Murray-Zmijewski F, Lane DP and Bourdon JC (2006) p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Differ 13, 962-972   DOI   ScienceOn
5 Melino G, De Laurenzi V and Vousden KH (2002) p73: Friend or foe in tumorigenesis. Nat Rev Cancer 2, 605-615   DOI   ScienceOn
6 Munarriz E, Bano D, Sayan AE, Rossi M, Melino G and Nicotera P (2005) Calpain cleavage regulates the protein stability of p73. Biochem Biophys Res Commun 333, 954-960   DOI   ScienceOn
7 Asher G, Tsvetkov P, Kahana C and Shaul Y (2005) A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73. Genes Dev 19, 316-321   DOI   ScienceOn
8 Rossi M, De Laurenzi V, Munarriz E et al (2005) The ubiquitin-protein ligase Itch regulates p73 stability. EMBO J 24, 836-848   DOI   ScienceOn
9 Oberst A, Malatesta M, Aqeilan RI et al (2007) The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch. Proc Natl Acad Sci U S A 104, 11280-11285   DOI   ScienceOn
10 Taebunpakul P, Sayan BS, Flinterman M et al (2012) Apoptin induces apoptosis by changing the equilibrium between the stability of TAp73 and DeltaNp73 isoforms through ubiquitin ligase PIR2. Apoptosis 17, 762-776   DOI   ScienceOn
11 Rao MA, Cheng H, Quayle AN, Nishitani H, Nelson CC and Rennie PS (2002) RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor. J Biol Chem 277, 48020-48027   DOI   ScienceOn
12 Sayan AE, Sayan BS, Gogvadze V et al (2008) P73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis. Oncogene 27, 4363-4372   DOI   ScienceOn
13 Chang NS, Pratt N, Heath J et al (2001) Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity. J Biol Chem 276, 3361-3370   DOI   ScienceOn
14 Terrasson J, Allart S, Martin H et al (2005) p73-dependent apoptosis through death receptor: impairment by human cytomegalovirus infection. Cancer Res 65, 2787-2794   DOI   ScienceOn
15 Kramer S, Ozaki T, Miyazaki K et al (2005) Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells. Oncogene 24, 938-944   DOI   ScienceOn
16 Deng Y and Wu X (2000) Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria. Proc Natl Acad Sci U S A 97, 12050-12055   DOI   ScienceOn
17 Schilling T, Schleithoff ES, Kairat A et al (2009) Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family. Biochem Biophys Res Commun 387, 399-404   DOI   ScienceOn
18 Aqeilan RI, Pekarsky Y, Herrero JJ et al (2004) Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc Natl Acad Sci U S A 101, 4401-4406   DOI   ScienceOn
19 John K, Alla V, Meier C and Pützer BM (2011) GRAMD4 mimics p53 and mediates the apoptotic function of p73 at mitochondria. Cell Death Differ 18, 874-886   DOI   ScienceOn
20 Inoue T, Stuart J, Leno R and Maki CG (2002) Nuclear import and export signals in control of the p53-related protein p73. J Biol Chem 277, 15053-15060   DOI   ScienceOn
21 Liu T, Roh SE, Woo JA, Ryu H and Kang DE (2013) Cooperative role of RanBP9 and P73 in mitochondriamediated apoptosis. Cell Death Dis 4, e476   DOI   ScienceOn
22 Atabakhsh E, Bryce DM, Lefebvre KJ and Schild-Poulter C (2009) RanBPM has proapoptotic activities that regulate cell death pathways in response to DNA damage. Mol Cancer Res 7, 1962-1972   DOI   ScienceOn
23 Bullock AN, Henckel J and Fersht AR (2000) Quantitative analysis of residual folding and DNA binding in mutant p53 core domain: definition of mutant states for rescue in cancer therapy. Oncogene 19, 1245-1256   DOI
24 Kussie PH, Gorina S, Marechal V et al (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274, 948-953   DOI   ScienceOn
25 Canning P, von Delft F and Bullock AN (2012) Structural basis for ASPP2 recognition by the tumor suppressor p73. J Mol Biol 423, 515-527   DOI   ScienceOn
26 Ethayathulla AS, Tse PW and Monti P (2012) Structure of p73 DNA-binding domain tetramer modulates p73 transactivation. Proc Natl Acad Sci U S A 109, 6066-6071   DOI
27 Joerger AC, Rajagopalan S, Natan E, Veprintsev DB, Robinson CV and Fersht AR (2009) Structural evolution of p53, p63, and p73: implication for heterotetramer formation. Proc Natl Acad Sci U S A 106, 17705-17710   DOI   ScienceOn
28 Chi SW, Ayed A and Arrowsmith CH (1999) Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain. EMBO J 18, 4438-4445   DOI   ScienceOn
29 Melino G, Bernassola F, Ranalli M et al (2004) p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial translocation. J Biol Chem 279, 8076-8083   DOI   ScienceOn
30 Thanos CD, Goodwill KE and Bowie JU (1999) Oligomeric structure of the human EphB2 receptor SAM domain. Science 283, 833-836   DOI   ScienceOn
31 Stapleton D, Balan I, Pawson T and Sicheri F (1999) The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization. Nat Struct Biol 6, 44-49   DOI   ScienceOn
32 Ha JH, Shin JS, Yoon MK et al (2013) Dual-site interactions of p53 protein transactivation domain with anti-apoptotic Bcl-2 family proteins reveal a highly convergent mechanism of divergent p53 pathways. J Biol Chem 288, 7387-7398   DOI   ScienceOn
33 Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ and Green DR (2010) The BCL-2 family reunion. Mol Cell 37, 299- 310   DOI   ScienceOn
34 Chi SW (2014) Structural insights into the transcription-independent apoptotic pathway of p53. BMB Rep 47, 167-172   DOI   ScienceOn
35 Chipuk JE, Bouchier-Hayes L and Green DR (2006) Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ 13, 1396-1402   DOI   ScienceOn
36 Ha JH, Won EY, Shin JS et al (2011) Molecular mimicry-based repositioning of nutlin-3 to anti-apoptotic Bcl-2 family proteins. J Am Chem Soc 133, 1244-1247   DOI   ScienceOn
37 Lee DH, Ha JH, Kim Y et al (2014) A Conserved Mechanism for Binding of p53 DNA-Binding Domain and Anti-Apoptotic Bcl-2 Family Proteins. Mol Cells 37, 264-269   DOI   ScienceOn
38 Bell S, Klein C, Muller L, Hansen S and Buchner J (2002) p53 contains large unstructured regions in its native state. J Mol Biol 322, 917-927   DOI   ScienceOn
39 Chi SG, Chang SG, Lee SJ, Lee CH, Kim JI and Park JH (1999) Elevated and biallelic expression of p73 is associated withprogression of human bladder cancer. Cancer Res 59, 2791-2793
40 Burge S, Teufel DP, Townsley FM, Freund SM, Bycroft M, Fersht AR (2009) Molecular basis of the interactions between the p73 N terminus and p300: effects on transactivation and modulation by phosphorylation. Proc Natl Acad Sci U S A 106, 3142-3147   DOI   ScienceOn
41 Casciano I, Mazzocco K, Boni L et al (2002) Expression of DeltaNp73 is a molecular marker for adverse outcome in neuroblastoma patients. Cell Death Differ 9, 246-251   DOI
42 Liu G, Xia T and Chen X (2003) The activation domains, the proline-rich domain, and the C-terminal basic domain in p53 are necessary for acetylation of histones on the proximal p21 promoter and interaction with p300/CREBbinding protein. J Biol Chem 278, 17557-17565   DOI   ScienceOn
43 Shin JS, Ha JH, Lee DH et al (2015) Structural convergence of unstructured p53 family transactivation domains in MDM2 recognition. Cell Cycle 14, 533-543   DOI
44 Moll UM and Slade N (2004) p63 and p73: roles in development and tumor formation. Mol Cancer Res 2, 371-386
45 Jost CA, Marin MC and Kaelin WG Jr (1997) p73 is a simian [correction of human] p53-related protein that can induce apoptosis. Nature 389, 191-194   DOI   ScienceOn
46 Miyashita T and Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80, 293-299   DOI   ScienceOn
47 Nakano K and Vousden KH (2001) PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 7, 683-694   DOI   ScienceOn
48 Oda E, Ohki R, Murasawa H et al (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288, 1053-1058   DOI   ScienceOn
49 Müller M, Wilder S, Bannasch D et al (1998) p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J Exp Med 188, 2033-2045   DOI
50 Mihara M, Erster S, Zaika A et al (2003) p53 has a direct apoptogenic role at the mitochondria. Mol Cell 11, 577-590   DOI   ScienceOn
51 Mantovani F, Piazza S, Gostissa M et al (2004) Pin1 links the activities of c-Abl and p300 in regulating p73 function. Mol Cell 14, 625-636   DOI   ScienceOn
52 Chipuk JE, Kuwana T, Bouchier-Hayes L et al (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303, 1010-1014   DOI   ScienceOn
53 Levy D, Adamovich Y, Reuven N and Shaul Y (2007) The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell Death Differ 14, 743-751   DOI   ScienceOn
54 Costanzo A, Merlo P, Pediconi N et al (2002) DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes. Mol Cell 9, 175-186   DOI   ScienceOn
55 Sayan BS, Yang AL, Conforti F et al (2010) Differential control of TAp73 and DeltaNp73 protein stability by the ring finger ubiquitin ligase PIR2. Proc Natl Acad Sci U S A 107, 12877-12882   DOI   ScienceOn
56 Danovi SA, Rossi M, Gudmundsdottir K, Yuan M, Melino G and Basu S (2008) Yes-associated protein (YAP) is a critical mediator of c-Jun-dependent apoptosis. Cell Death Differ 15, 217-219   DOI   ScienceOn
57 Dulloo I, Gopalan G, Melino G and Sabapathy K (2010) The antiapoptotic DeltaNp73 is degraded in a c-Jun-dependent manner upon genotoxic stress through the antizyme-mediated pathway. Proc Natl Acad Sci U S A 107, 4902-4907   DOI   ScienceOn
58 Ramadan S, Terrinoni A, Catani MV et al (2005) p73 induces apoptosis by different mechanisms. Biochem Biophys Res Commun 331, 713-717   DOI   ScienceOn
59 Zaika AI, Slade N, Erster SH et al (2002) DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up-regulated in human tumors. J Exp Med 196, 765-780   DOI
60 Chipuk JE, Bouchier-Hayes L, Kuwana T, Newmeyer DD and Green DR (2005) PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309, 1732-1735   DOI   ScienceOn
61 Toh WH, Siddique MM, Boominathan L, Lin KW and Sabapathy K (2004) c-Jun regulates the stability and activity of the p53 homologue, p73. J Biol Chem 279, 44713-44722   DOI   ScienceOn