title: Non genomic loss of function of tumor suppressors in CML: BCR-ABL promotes IκBα mediated p53 nuclear exclusion.
abstract: Tumor suppressor function can be modulated by subtle variation of expression levels, proper cellular compartmentalization and post-translational modifications, such as phosphorylation, acetylation and sumoylation. The non-genomic loss of function of tumor suppressors offers a challenging therapeutic opportunity. The reactivation of a tumor suppressor could indeed promote selective apoptosis of cancer cells without affecting normal cells. The identification of mechanisms that affect tumor suppressor functions is therefore essential. In this work, we show that BCR-ABL promotes the accumulation of the NFKBIA gene product, IκBα, in the cytosol through physical interaction and stabilization of the protein. Furthermore, BCR-ABL/IκBα complex acts as a scaffold protein favoring p53 nuclear exclusion. We therefore identify a novel BCR-ABL/IκBα/p53 network, whereby BCR-ABL functionally inactivates a key tumor suppressor.
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Sabrina
authors: S
authors: Crivellaro
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Cristina
authors: C
authors: Panuzzo
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Giovanna
authors: G
authors: Carrà
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Alessandro
authors: A
authors: Volpengo
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Francesca
authors: F
authors: Crasto
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Enrico
authors: E
authors: Gottardi
authors: Division of Pathology, Department of Oncology, University of Turin at St Luigi Hospital, Torino, Italy.
authors: Ubaldo
authors: U
authors: Familiari
authors: Division of Pathology, Department of Oncology, University of Turin at St Luigi Hospital, Torino, Italy.
authors: Mauro
authors: M
authors: Papotti
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Davide
authors: D
authors: Torti
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Rocco
authors: R
authors: Piazza
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Sara
authors: S
authors: Redaelli
authors: Department of Oncology, University of Turin, Turin, Italy.
authors: Riccardo
authors: R
authors: Taulli
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Angelo
authors: A
authors: Guerrasio
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Giuseppe
authors: G
authors: Saglio
authors: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors: Alessandro
authors: A
authors: Morotti
mesh_terms: D021581:Active Transport, Cell Nucleus; D003600:Cytosol / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046912:Multiprotein Complexes; D000072000:NF-KappaB Inhibitor alpha; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C581634:BCR-ABL1 fusion protein, human; D020672:I-kappa B Proteins; D046912:Multiprotein Complexes; C000606204:NFKBIA protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000072000:NF-KappaB Inhibitor alpha; D016044:Fusion Proteins, bcr-abl
keywords: IκBα; NF-κB; chronic myeloid leukemia; p53; tumor suppressor