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

Luana D'Artista, Andrea Bisso, Andrea Piontini, Mirko Doni, Alessandro Verrecchia, Theresia R. Kress, Marco J. Morelli, Giannino Del Sal, Bruno Amati, Stefano Campaner

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)21786-21798
Number of pages13
JournalOncotarget
Volume7
Issue number16
DOIs
Publication statusPublished - Apr 19 2016

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B-Lymphocytes
Phosphorylation
Cell Proliferation
Peptidylprolyl Isomerase
myc Genes
Burkitt Lymphoma
Mitogens
Codon
Transgenic Mice
Disease Progression
Lymphoma
Cell Cycle
Apoptosis
Neoplasms
Proteins
Therapeutics

Keywords

  • C-myc
  • Lymphoma
  • Pin1
  • Proliferation

ASJC Scopus subject areas

  • Oncology

Cite this

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.

In: Oncotarget, Vol. 7, No. 16, 19.04.2016, p. 21786-21798.

Research output: Contribution to journalArticle

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. In: Oncotarget. 2016 ; Vol. 7, No. 16. pp. 21786-21798.
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