Cargando…

Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc

The c-myc proto-oncogene is activated by translocation in Burkitt's lymphoma and substitutions in codon 58 stabilize the Myc protein or augment its oncogenic potential. In wild-type Myc, phosphorylation of Ser 62 and Thr 58 provides a landing pad for the peptidyl prolyl-isomerase Pin1, which in...

Descripción completa

Detalles Bibliográficos
Autores principales: D'Artista, Luana, Bisso, Andrea, Piontini, Andrea, Doni, Mirko, Verrecchia, Alessandro, Kress, Theresia R., Morelli, Marco J., Del Sal, Giannino, Amati, Bruno, Campaner, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008323/
https://www.ncbi.nlm.nih.gov/pubmed/26943576
http://dx.doi.org/10.18632/oncotarget.7846
_version_ 1782451348712718336
author D'Artista, Luana
Bisso, Andrea
Piontini, Andrea
Doni, Mirko
Verrecchia, Alessandro
Kress, Theresia R.
Morelli, Marco J.
Del Sal, Giannino
Amati, Bruno
Campaner, Stefano
author_facet D'Artista, Luana
Bisso, Andrea
Piontini, Andrea
Doni, Mirko
Verrecchia, Alessandro
Kress, Theresia R.
Morelli, Marco J.
Del Sal, Giannino
Amati, Bruno
Campaner, Stefano
author_sort D'Artista, Luana
collection PubMed
description The c-myc proto-oncogene is activated by translocation in Burkitt's lymphoma and substitutions in codon 58 stabilize the Myc protein or augment its oncogenic potential. In wild-type Myc, phosphorylation of Ser 62 and Thr 58 provides a landing pad for the peptidyl prolyl-isomerase Pin1, which in turn promotes Ser 62 dephosphorylation and Myc degradation. However, the role of Pin1 in Myc-induced lymphomagenesis remains unknown. We show here that genetic ablation of Pin1 reduces lymphomagenesis in Eμ-myc transgenic mice. In both Pin1-deficient B-cells and MEFs, the proliferative response to oncogenic Myc was selectively impaired, with no alterations in Myc-induced apoptosis or mitogen-induced cell cycle entry. This proliferative defect wasn't attributable to alterations in either Ser 62 phosphorylation or Myc-regulated transcription, but instead relied on the activity of the ARF-p53 pathway. Pin1 silencing in lymphomas retarded disease progression in mice, making Pin1 an attractive therapeutic target in Myc-driven tumors.
format Online
Article
Text
id pubmed-5008323
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-50083232016-09-12 Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc D'Artista, Luana Bisso, Andrea Piontini, Andrea Doni, Mirko Verrecchia, Alessandro Kress, Theresia R. Morelli, Marco J. Del Sal, Giannino Amati, Bruno Campaner, Stefano Oncotarget Research Paper The c-myc proto-oncogene is activated by translocation in Burkitt's lymphoma and substitutions in codon 58 stabilize the Myc protein or augment its oncogenic potential. In wild-type Myc, phosphorylation of Ser 62 and Thr 58 provides a landing pad for the peptidyl prolyl-isomerase Pin1, which in turn promotes Ser 62 dephosphorylation and Myc degradation. However, the role of Pin1 in Myc-induced lymphomagenesis remains unknown. We show here that genetic ablation of Pin1 reduces lymphomagenesis in Eμ-myc transgenic mice. In both Pin1-deficient B-cells and MEFs, the proliferative response to oncogenic Myc was selectively impaired, with no alterations in Myc-induced apoptosis or mitogen-induced cell cycle entry. This proliferative defect wasn't attributable to alterations in either Ser 62 phosphorylation or Myc-regulated transcription, but instead relied on the activity of the ARF-p53 pathway. Pin1 silencing in lymphomas retarded disease progression in mice, making Pin1 an attractive therapeutic target in Myc-driven tumors. Impact Journals LLC 2016-03-02 /pmc/articles/PMC5008323/ /pubmed/26943576 http://dx.doi.org/10.18632/oncotarget.7846 Text en Copyright: © 2016 D'Artista et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
D'Artista, Luana
Bisso, Andrea
Piontini, Andrea
Doni, Mirko
Verrecchia, Alessandro
Kress, Theresia R.
Morelli, Marco J.
Del Sal, Giannino
Amati, Bruno
Campaner, Stefano
Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc
title Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc
title_full Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc
title_fullStr Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc
title_full_unstemmed Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc
title_short Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc
title_sort pin1 is required for sustained b cell proliferation upon oncogenic activation of myc
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008323/
https://www.ncbi.nlm.nih.gov/pubmed/26943576
http://dx.doi.org/10.18632/oncotarget.7846
work_keys_str_mv AT dartistaluana pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT bissoandrea pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT piontiniandrea pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT donimirko pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT verrecchiaalessandro pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT kresstheresiar pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT morellimarcoj pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT delsalgiannino pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT amatibruno pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc
AT campanerstefano pin1isrequiredforsustainedbcellproliferationupononcogenicactivationofmyc