EEC- and ADULT-Associated TP63 Mutations Exhibit Functional Heterogeneity Toward P63 Responsive Sequences

Human Mutation

Volumn 34, Issue 6, 2013, Pages 894-904

  Monti, Paola ^a   Russo, Debora ^a   Bocciardi, Renata ^b,c   Foggetti, Giorgia ^a   Menichini, Paola ^a   Divizia, Maria T ^b   Lerone, Margherita ^b   Graziano, Claudio ^d   Wischmeijer, Anita ^d,e   Viadiu, Hector ^f   Ravazzolo, Roberto ^b,c   Inga, Alberto ^g   Fronza, Gilberto ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b G GASLINI INSTITUTE   (Italy)

^c UNIVERSITY OF GENOA   (Italy)

^d UNIVERSITY OF BOLOGNA   (Italy)

^e S MARIA NUOVA HOSPITAL   (Italy)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g UNIVERSITY OF TRENTO   (Italy)

Author keywords

Ectodermal dysplasia; TP63; Transactivation; Yeast

Indexed keywords

COL18A1; COLLAGEN TYPE 1; PROTEIN BAX; PROTEIN MDM2; PROTEIN P21; PROTEIN P63; PUMA PROTEIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ACRODERMATOUNGUAL LACRIMAL TOOTH SYNDROME; ALLELE; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DNA BINDING MOTIF; ECTODERM; EEC SYNDROME; GENE; GENE MUTATION; GENE SEQUENCE; GENETIC HETEROGENEITY; GENETIC IDENTIFICATION; HUMAN; HUMAN CELL; NONHUMAN; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DOMAIN; SACCHAROMYCES CEREVISIAE; SYNDROME; TEMPERATURE SENSITIVITY; TP63 GENE; TRANSACTIVATION;

ALLELES; AMINO ACID SUBSTITUTION; ANODONTIA; APOPTOSIS REGULATORY PROTEINS; BCL-2-ASSOCIATED X PROTEIN; BREAST; CELL LINE; CLEFT LIP; CLEFT PALATE; ECTODERMAL DYSPLASIA; GENE EXPRESSION REGULATION; GENETIC ASSOCIATION STUDIES; GERM-LINE MUTATION; HCT116 CELLS; HUMANS; LACRIMAL DUCT OBSTRUCTION; LIMB DEFORMITIES, CONGENITAL; MUTATION; NAILS, MALFORMED; PHENOTYPE; PIGMENTATION DISORDERS; PROTEIN ISOFORMS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; RESPONSE ELEMENTS; TRANS-ACTIVATORS; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEIN P53; TUMOR SUPPRESSOR PROTEINS; YEASTS;

MAMMALIA;

EID: 84878116430     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22304     Document Type: Article

References (60)

1. Andreotti V, Ciribilli Y, Monti P, Bisio A, Lion M, Jordan J, Fronza G, Menichini P, Resnick MA, Inga A. 2011. p53 transactivation and the impact of mutations, cofactors and small molecules using a simplified yeast-based screening system. PLoS ONE 6:e20643.
2. Avitan-Hersh E, Indelman M, Bergman R, Sprecher E. 2010. ADULT syndrome caused by a mutation previously associated with EEC syndrome. Pediatr Dermatol 27:643-645.
3. Beyer U, Moll-Rocek J, Moll UM, Dobbelstein M. 2011. Endogenous retrovirus drives hitherto unknown proapoptotic p63 isoforms in the male germ line of humans and great apes. Proc Natl Acad Sci USA 108:3624-3629.
4. Browne G, Cipollone R, Lena AM, Serra V, Zhou H, van Bokhoven H, Dötsch V, Merico D, Mantovani R, Terrinoni A, Knight RA, Candi E, et al. 2011. Differential altered stability and transcriptional activity of ΔNp63 mutants in distinct ectodermal dysplasias. J Cell Sci 124:2200-2207.
5. Candi E, Cipollone R, Rivetti di Val Cervo P, Gonfloni S, Melino G, Knight R. 2008. p63 in epithelial development. Cell Mol Life Sci 65:3126-3133.
6. Candi E, Rufini A, Terrinoni A, Dinsdale D, Ranalli M, Paradisi A, DeLaurenzi V, Spagnoli LG, Catani MV, Ramadan S, Knight RA, Melino G. 2006. Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ 13:1037-1047.
7. Celik TH, Buyukcam A, Simsek-Kiper PO, Utine GE, Ersoy-Evans S, Korkmaz A, Yntema HG, Bodugroglu K, Yurdakok M. 2011. A newborn with overlapping features of AEC and EEC syndromes. Am J Med Genet A 155A:3100-3103.
8. Celli J, Duijf P, Hamel BC, Bamshad M, Kramer B, Smits AP, Newbury-Ecob R, Hennekam RC, Van Buggenhout G, van Haeringen A, Woods CG, van Essen AJ, et al. 1999. Heterozygous germ line mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell 99:143-153.
9. Chen C, Gorlatova N, Kelman Z, Herzberg O. 2011. Structures of p63 DNA binding domain in complexes with half-site and with spacer-containing full response elements. Proc Natl Acad Sci USA 108:6456-6461.
10. Chung J, Grant RI, Kaplan DR, Irwin MS. 2011. Special AT-rich binding protein-2 (SATB2) differentially affects disease-causing p63 mutant proteins. J Biol Chem 286:40671-40680.
11. Dohn M, Zhang S, Chen X. 2001. p63alpha and DeltaNp63alpha can induce cell cycle arrest and apoptosis and differentially regulate p53 target genes. Oncogene 20:3193-3205.
12. Duijf PH, Vanmolkot KR, Propping P, Friedl W, Krieger E, McKeon F, Dötsch V, Brunner HG, van Bokhoven H. 2002. Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Hum Mol Genet 11:799-804.
13. Ethayathulla AS, Tse PW, Monti P, Nguyen S, Inga A, Fronza G, Viadiu H. 2012. Structure of p73 DNA-binding domain tetramer modulates p73 transactivation. Proc Natl Acad Sci USA 109:6066-6071.
14. Flaman JM, Frebourg T, Moreau V, Charbonnier F, Martin C, Chappuis P, Sappino AP, Limacher IM, Bron L, Benhattar J, Tada M, Van Meir EG, et al. 1995. A simple p53 functional assay for screening cell lines, blood, and tumors. Proc Natl Acad Sci USA 92:3963-3967.
15. Ghioni P, Bolognese F, Duijf PH, Van Bokhoven H, Mantovani R, Guerrini L. 2002. Complex transcriptional effects of TP63 isoforms: identification of novel activation and repression domains. Mol Cell Biol 22:8659-8668.
16. Gritli-Linde A. 2010. p63 and IRF6: brothers in arms against cleft palate. J Clin Invest 120:1386-1389.
17. Helton ES, Zhang J, Chen X. 2008. The proline-rich domain in p63 is necessary for the transcriptional and apoptosis-inducing activities of TAp63. Oncogene 27:2843-2850.
18. Ihrie RA, Bronson RT, Attardi LD. 2006. Adult mice lacking the p53/p63 target gene Perp are not predisposed to spontaneous tumorigenesis but display features of ectodermal dysplasia syndromes. Cell Death Differ 13:1614-1618.
19. Ihrie RA, Marques MR, Nguyen BT, Horner JS, Papazoglu C, Bronson RT, Mills AA, Attardi LD. 2005. Perp is a p63-regulated gene essential for epithelial integrity. Cell 120:843-856
20. Inga A, Cresta S, Monti P, Aprile A, Scott G, Abbondandolo A, Iggo R, Fronza G. 1997. Simple identification of dominant p53 mutants by a yeast functional assay. Carcinogenesis 18:2019-2021.
21. Inga A, Monti P, Fronza G, Darden T, Resnick MA. 2001. p53 mutants exhibiting enhanced transcriptional activation and altered promoter selectivity are revealed using a sensitive, yeast-based functional assay. Oncogene 20:501-513.
22. Inga A, Storici F, Darden TA, Resnick MA. 2002. Differential transactivation by the p53 transcription factor is highly dependent on p53 level and promoter target sequence. Mol Cell Biol 22:8612-8625.
23. Kelley LA, Sternberg MJ. 2009. Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 4:363-371.
24. Khokhar SK, Kommagani R, Kadakia MP. 2008. Differential effects of p63 mutants on transactivation of p53 and/or p63 responsive genes. Cell Res 18:1061-1073.
25. Kier-Swiatecka E, Kock M, Marker P, Eiberg H, Kjaer KW. 2007. The ADULT-EEC spectrum: an R280C mutation with a borderline phenotype. Am J Med Genet A 143A:891-894.
26. Kirschner RD, Rother K, Müller GA, Engeland K. 2010. The retinal dehydrogenase/reductase retSDR1/DHRS3 gene is activated by p53 and p63 but not by mutants derived from tumors or EEC/ADULT malformation syndromes. Cell Cycle 9:2177-2188.
27. Kouwenhoven EN, van Heeringen SJ, Tena JJ, Oti M, Dutilh BE, Alonso ME, de la Calle-Mustienes E, Smeenk L, Rinne T, Parsaulian L, Bolat E, Jurgelenaite R, et al. 2010. Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus. PLoS Genet 6:e1001065.
28. Krivov GG, Shapovalov MV, Dunbrack RL Jr. 2009. Improved prediction of protein side-chain conformations with SCWRL4. Proteins 77:778-795.
29. Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. 2011. The p53 family: guardians of maternal reproduction. Nat Rev Mol Cell Biol 12:259-265.
30. Lo Iacono M, Di Costanzo A, Calogero RA, Mansueto G, Saviozzi S, Crispi S, Pollice A, La Mantia G, Calabrò V. 2006. The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity. Cell Cycle 5:78-87.
31. Lo Iacono N, Mantero S, Chiarelli A, Garcia E, Mills AA, Morasso MI, Costanzo A, Levi G, Guerrini L, Merlo GR. 2008. Regulation of Dlx5 and Dlx6 gene expression by p63 is involved in EEC and SHFM congenital limb defects. Development 135:1377-1388.
32. Mangiulli M, Valletti A, Caratozzolo MF, Tullo A, Sbisà E, Pesole G, D'Erchia AM. 2009. Identification and functional characterization of two new transcriptional variants of the human p63 gene. Nucleic Acids Res 37:6092-6104.
33. McKeon F. 2004. p63 and the epithelial stem cell: more than status quo? Genes Dev 18:465-469.
34. Melino G. 2011. p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53. Cell Death Differ 18:1487-1499.
35. Monti P, Ciribilli Y, Jordan J, Menichini P, Umbach DM, Resnick MA, Luzzatto L, Inga A, Fronza G. 2007. Transcriptional functionality of germ line p53 mutants influences cancer phenotype. Clin Cancer Res 13:3789-3795.
36. Monti P, Perfumo C, Bisio A, Ciribilli Y, Menichini P, Russo D, Umbach DM, Resnick MA, Inga A, Fronza G. 2011. Dominant-negative features of mutant p53 in germ line carriers have limited impact on cancer outcomes. Mol Cancer Res 9:271-279.
37. Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M, Ikawa S. 1998. Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Nat Med 4:839-843.
38. Petre-Lazar B, Livera G, Moreno SG, Trautmann E, Duquenne C, Hanoux V, Habert R, Coffigny H. 2007. The role of p63 in germ cell apoptosis in the developing testis. J Cell Physiol 210:87-98.
39. Prontera P, Escande F, Cocchi G, Donti E, Martini A, Sensi A. 2008. An intermediate phenotype between Hay-Wells and Rapp-Hodgkin syndromes in a patient with a novel P63 mutation: confirmation of a variable phenotypic spectrum with a common aetiology. Genet Couns 19:397-402.
40. Prontera P, Garelli E, Isidori I, Mencarelli A, Carando A, Silengo MC, Donti E. 2011. Cleft palate and ADULT phenotype in a patient with a novel TP63 mutation suggests lumping of EEC/LM/ADULT syndromes into a unique entity: ELA syndrome. Am J Med Genet A 155A:2746-2749.
41. Pyati UJ, Gjini E, Carbonneau S, Lee JS, Guo F, Jette CA, Kelsell DP, Look AT. 2011. p63 mediates an apoptotic response to pharmacological and disease-related ER stress in the developing epidermis. Dev Cell 21:492-505.
42. Resnick MA, Inga A. 2003. Functional mutants of the sequence-specific transcription factor p53 and implications for master genes of diversity. Proc Natl Acad Sci USA 100:9934-9939.
43. Rinne T, Brunner HG, van Bokhoven H. 2007. p63-associated disorders. Cell Cycle 6:262-268.
44. Rinne T, Spadoni E, Kjaer KW, Danesino C, Larizza D, Kock M, Huoponen K, Savontaus ML, Aaltonen M, Duijf P, Brunner HG, Penttinen M, et al. 2006. Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene. Eur J Hum Genet 14:904-910.
45. Rökaeus N, Shen J, Eckhardt I, Bykov VJ, Wiman KG, Wilhelm MT. 2010. PRIMA-1(MET)/APR-246 targets mutant forms of p53 family members p63 and p73. Oncogene 29:6442-6451.
46. Sawardekar SS, Zaenglein AL. 2011. Ankyloblepharon-ectodermal dysplasia-clefting syndrome: a novel p63 mutation associated with generalized neonatal erosions. Pediatr Dermatol 28:313-317.
47. Serra V, Castori M, Paradisi M, Bui L, Melino G, Terrinoni A. 2011. Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp-Hodgkin/AEC/ADULT syndromes. Am J Med Genet A 155A:3104-3109.
48. Shalom-Feuerstein R, Lena AM, Zhou H, De La Forest Divonne S, Van Bokhoven H, Candi E, Melino G, Aberdam D. 2011. ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis. Cell Death Differ 18:887-896.
49. Shimada A, Kato S, Enjo K, Osada M, Ikawa Y, Kohno K, Obinata M, Kanamaru R, Ikawa S, Ishioka C. 1999. The transcriptional activities of p53 and its homologue p51/p63: similarities and differences. Cancer Res 59:2781-2786.
50. Slavotinek AM, Tanaka J, Winder A, Vargervik K, Haggstrom A, Bamshad M. 2005. Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome: report of a child with phenotypic overlap with ulnar-mammary syndrome and a new mutation in TP63. Am J Med Genet A 138A:146-149.
51. Storici F, Resnick MA. 2003. Delitto perfetto targeted mutagenesis in yeast with oligonucleotides. Genet Eng (NY) 25:189-207.
52. Suh EK, Yang A, Kettenbanch A, Bamberger C, Michaelis AH, Zhu Z, Elvin JA, Bronson RT, Crum CP, Mckeon F. 2006. p63 protects the female germ line during meiotic arrest. Nature 444:624-628.
53. Tsunoda T, Takagi T. 1999. Estimating transcription factor bindability on DNA. Bioinformatics 15:622-630.
54. Utriainen A, Sormunen R, Kettunen M, Carvalhaes LS, Sajanti E, Eklund L, Kauppinen R, Kitten GT, Pihlajaniemi T. 2004. Structurally altered basement membranes and hydrocephalus in a type XVIII collagen deficient mouse line. Hum Mol Genet 13:2089-2099.
55. van Bokhoven H, Hamel BC, Bamshad M, Sangiorgi E, Gurrieri F, Duijf PH, Vanmolkot KR, van Beusekom E, van Beersum SE, Celli J, Merkx GF, Tenconi R, et al. 2001. p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation. Am J Hum Genet 69:481-492.
56. van Bokhoven H, Melino G, Candi E, Declercq W. 2011. p63, a story of mice and men. J Invest Dermatol 131:1196-1207.
57. Vera-Carbonell A, Moya-Quiles MR, Ballesta-Martínez M, López-González V, Bafallíu JA, Guillén-Navarro E, López-Expósito I. 2012. Rapp-Hodgkin syndrome and SHFM1 patients: delineating the p63-Dlx5/Dlx6 pathway. Gene 497:292-297.
58. Vilgelm AE, Washington MK, Wei J, Chen H, Prassolov VS, Zaika AI. 2010. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors. Mol Cancer Ther 9:693-705.
59. Westfall MD, Mays DJ, Sniezek JC, Pietenpol JA. 2003. The Delta Np63 alpha phosphoprotein binds the p21 and 14-3-3 sigma promoters in vivo and has transcriptional repressor activity that is reduced by Hay-Wells syndrome-derived mutations. Mol Cell Biol 23:2264-2276.
60. Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dötsch V, Andrews NC, Caput D, McKeon F. 1998. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2:305-316.