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14-3-3 Ligand Prevents Nuclear Import of c-ABL Protein in Chronic Myeloid Leukemia
dc.creator | Mancini, Manuela | |
dc.creator | Veljković, Nevena V. | |
dc.creator | Corradi, Valentina | |
dc.creator | Zuffa, Elisa | |
dc.creator | Corrado, Patrizia | |
dc.creator | Pagnotta, Eleonora | |
dc.creator | Martinelli, Giovanni | |
dc.creator | Barbieri, Enza | |
dc.creator | Santucci, Maria Alessandra | |
dc.date.accessioned | 2018-03-01T20:47:37Z | |
dc.date.available | 2018-03-01T20:47:37Z | |
dc.date.issued | 2009 | |
dc.identifier.issn | 1398-9219 | |
dc.identifier.uri | https://vinar.vin.bg.ac.rs/handle/123456789/3700 | |
dc.description.abstract | Here we demonstrated that the loss of function of not-rearranged c-ABL in chronic myeloid leukemia (CML) is promoted by its cytoplasmic compartmentalization bound to 14-3-3 sigma scaffolding protein. In particular, constitutive tyrosine kinase (TK) activity of p210 BCR-ABL blocks c-Jun N-terminal kinase (JNK) phosphorylation leading to 14-3-3 sigma phosphorylation at a critical residue (Ser(186)) for c-ABL binding in response to DNA damage. Moreover, it is associated with 14-3-3 sigma over-expression arising from epigenetic mechanisms (promoter hyper-acetylation). Accordingly, p210 BCR-ABL TK inhibition by the TK inhibitor Imatinib mesylate (IM) evokes multiple events, including JNK phosphorylation at Thr(183), p38 mitogen-activated protein kinase (MAPK) phosphorylation at Thr(180), c-ABL de-phosphorylation at Ser residues involved in 14-3-3 binding and reduction of 14-3-3 sigma expression, that let c-ABL release from 14-3-3 sigma and nuclear import, and address BCR-ABL-expressing cells towards apoptotic death. Informational spectrum method (ISM), a virtual spectroscopy method for analysis of protein interactions based on their structure, and mathematical filtering in cross spectrum (CS) analysis identified 14-3-3 sigma/c-ABL binding sites. Further investigation on CS profiles of c-ABL- and p210 BCR-ABL-containing complexes revealed the mechanism likely involved 14-3-3 precluded phosphorylation in CML cells. | en |
dc.relation | University of Bologna, BolognaAIL and Carisbo Foundation, Dipartimento di Scienze Radiologiche e Istocitopatologiche, Centro Interdipartimentale di Ricerca sul Cancro Giorgio Prodi | |
dc.rights | openAccess | en |
dc.source | Traffic | en |
dc.subject | Chronic Myeloid Leukemia (CML) | en |
dc.subject | BCR-ABL | en |
dc.subject | Imatinib mesylate (IM) | en |
dc.subject | c-ABL | en |
dc.subject | 14-3-3 sigma | en |
dc.subject | JNK | en |
dc.subject | p38 MAPK | en |
dc.title | 14-3-3 Ligand Prevents Nuclear Import of c-ABL Protein in Chronic Myeloid Leukemia | en |
dc.type | article | en |
dcterms.abstract | Цоррадо, Патризиа; Мартинелли, Гиованни; Барбиери, Енза; Сантуцци, Мариа Aлессандра; Цорради, Валентина; Зуффа, Елиса; Манцини, Мануела; Вељковић Невена В.; Пагнотта, Елеонора; | |
dc.citation.volume | 10 | |
dc.citation.issue | 6 | |
dc.citation.spage | 637 | |
dc.citation.epage | 647 | |
dc.identifier.wos | 000266113000004 | |
dc.identifier.doi | 10.1111/j.1600-0854.2009.00897.x | |
dc.citation.rank | M21 | |
dc.identifier.pmid | 19220809 | |
dc.identifier.scopus | 2-s2.0-65749098409 | |
dc.identifier.fulltext | https://vinar.vin.bg.ac.rs//bitstream/id/4836/j.1600-0854.2009.00897.x.pdf |