title: Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc.
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.
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.|Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: D'Artista
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bisso
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Piontini
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Doni
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Verrecchia
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
authors.forename: Theresia R
authors.initials: TR
authors.lastname: Kress
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Morelli
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste, Italy.|Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy.
authors.forename: Giannino
authors.initials: G
authors.lastname: Del Sal
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.|Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Amati
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Campaner
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016271:Proto-Oncogene Proteins c-myc
keywords: Pin1; c-myc; lymphoma; proliferation