A nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins

Emilia Coppari,1 Tohru Yamada,2 Anna Rita Bizzarri,1 Craig W Beattie,2 Salvatore Cannistraro1 1Biophysics and Nanoscience Centre, CNISM-DEB, Università della Tuscia, Viterbo, Italy; 2Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Coppari E, Yamada T, Bizzarri AR, Beattie CW, Cannistraro S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f8207735f69745c2a47e9357f763904d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f8207735f69745c2a47e9357f763904d
record_format	dspace
spelling	oai:doaj.org-article:f8207735f69745c2a47e9357f763904d2021-12-02T01:32:50ZA nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins1178-2013https://doaj.org/article/f8207735f69745c2a47e9357f763904d2014-04-01T00:00:00Zhttp://www.dovepress.com/a-nanotechnological-molecular-modeling-and-immunological-approach-to-s-a16427https://doaj.org/toc/1178-2013 Emilia Coppari,1 Tohru Yamada,2 Anna Rita Bizzarri,1 Craig W Beattie,2 Salvatore Cannistraro1 1Biophysics and Nanoscience Centre, CNISM-DEB, Università della Tuscia, Viterbo, Italy; 2Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, IL, USA Abstract: p28 is an anionic, amphipathic, cell-penetrating peptide derived from the cupredoxin azurin that binds to the DNA-binding domain (DBD) of the tumor suppressor protein, p53, and induces a post-translational increase in the level of wild type and mutated p53 in a wide variety of human cancer cells. As p63 and p73, additional members of the p53 superfamily of proteins, also appear to be involved in the cellular response to cancer therapy and are reportedly required for p53-induced apoptosis, we asked whether p28 also binds to p63 and p73. Atomic force spectroscopy demonstrates that p28 forms a stable, high-affinity complex with full-length p63, the DBD of p63, and full-length p73. Exposure to p28 decreased the level of TAp63α and ΔNp63α, the truncated form of p63, in p53 wild type and mutated human breast cancer cells, respectively. p28 increased the level of TAp73α, but not ΔNp73α, in the same breast cancer cell lines. In contrast, p28 increased the level of the TA and ΔN isoforms of p63 in p53 wild type, but not in p53 mutated melanoma cells, while decreasing TA p73α in p53 wild type and mutated human melanoma cells. All changes were mirrored by an associated change in the expression of the HECT E3 ligases Itch/AIP4, AIP5, and the RING E3 ligase Pirh2, but not in the receptor for activated C kinase or the RING E3 ligases Mdm2 and Cop1. Collectively, the data suggest that molecules such as p28 bind with high affinity to the DBD of p63 and p73 and alter their expression independent of the Mdm2 and Cop1 pathways. Keywords: molecular interaction, anticancer peptide, p53 superfamily of proteinsCoppari EYamada TBizzarri ARBeattie CWCannistraro SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 1799-1813 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Coppari E Yamada T Bizzarri AR Beattie CW Cannistraro S A nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins
description	Emilia Coppari,1 Tohru Yamada,2 Anna Rita Bizzarri,1 Craig W Beattie,2 Salvatore Cannistraro1 1Biophysics and Nanoscience Centre, CNISM-DEB, Università della Tuscia, Viterbo, Italy; 2Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, IL, USA Abstract: p28 is an anionic, amphipathic, cell-penetrating peptide derived from the cupredoxin azurin that binds to the DNA-binding domain (DBD) of the tumor suppressor protein, p53, and induces a post-translational increase in the level of wild type and mutated p53 in a wide variety of human cancer cells. As p63 and p73, additional members of the p53 superfamily of proteins, also appear to be involved in the cellular response to cancer therapy and are reportedly required for p53-induced apoptosis, we asked whether p28 also binds to p63 and p73. Atomic force spectroscopy demonstrates that p28 forms a stable, high-affinity complex with full-length p63, the DBD of p63, and full-length p73. Exposure to p28 decreased the level of TAp63α and ΔNp63α, the truncated form of p63, in p53 wild type and mutated human breast cancer cells, respectively. p28 increased the level of TAp73α, but not ΔNp73α, in the same breast cancer cell lines. In contrast, p28 increased the level of the TA and ΔN isoforms of p63 in p53 wild type, but not in p53 mutated melanoma cells, while decreasing TA p73α in p53 wild type and mutated human melanoma cells. All changes were mirrored by an associated change in the expression of the HECT E3 ligases Itch/AIP4, AIP5, and the RING E3 ligase Pirh2, but not in the receptor for activated C kinase or the RING E3 ligases Mdm2 and Cop1. Collectively, the data suggest that molecules such as p28 bind with high affinity to the DBD of p63 and p73 and alter their expression independent of the Mdm2 and Cop1 pathways. Keywords: molecular interaction, anticancer peptide, p53 superfamily of proteins
format	article
author	Coppari E Yamada T Bizzarri AR Beattie CW Cannistraro S
author_facet	Coppari E Yamada T Bizzarri AR Beattie CW Cannistraro S
author_sort	Coppari E
title	A nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins
title_short	A nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins
title_full	A nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins
title_fullStr	A nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins
title_full_unstemmed	A nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins
title_sort	nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/f8207735f69745c2a47e9357f763904d
work_keys_str_mv	AT copparie ananotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT yamadat ananotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT bizzarriar ananotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT beattiecw ananotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT cannistraros ananotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT copparie nanotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT yamadat nanotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT bizzarriar nanotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT beattiecw nanotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins AT cannistraros nanotechnologicalmolecularmodelingandimmunologicalapproachtostudytheinteractionoftheantitumorigenicpeptidep28withthep53familyofproteins
_version_	1718403051956469760

A nanotechnological, molecular-modeling, and immunological approach to study the interaction of the anti-tumorigenic peptide p28 with the p53 family of proteins

Ejemplares similares