14-3-3 Ligand Prevents Nuclear Import of c-ABL Protein in Chronic Myeloid Leukemia
Autori
Mancini, ManuelaVeljković, Nevena V.
Corradi, Valentina
Zuffa, Elisa
Corrado, Patrizia
Pagnotta, Eleonora
Martinelli, Giovanni
Barbieri, Enza
Santucci, Maria Alessandra
Članak u časopisu
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 cell...s 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.
Ključne reči:
Chronic Myeloid Leukemia (CML) / BCR-ABL / Imatinib mesylate (IM) / c-ABL / 14-3-3 sigma / JNK / p38 MAPKIzvor:
Traffic, 2009, 10, 6, 637-647Finansiranje / projekti:
- University of Bologna, BolognaAIL and Carisbo Foundation, Dipartimento di Scienze Radiologiche e Istocitopatologiche, Centro Interdipartimentale di Ricerca sul Cancro Giorgio Prodi
DOI: 10.1111/j.1600-0854.2009.00897.x
ISSN: 1398-9219
PubMed: 19220809
WoS: 000266113000004
Scopus: 2-s2.0-65749098409
Kolekcije
Institucija/grupa
VinčaTY - JOUR AU - Mancini, Manuela AU - Veljković, Nevena V. AU - Corradi, Valentina AU - Zuffa, Elisa AU - Corrado, Patrizia AU - Pagnotta, Eleonora AU - Martinelli, Giovanni AU - Barbieri, Enza AU - Santucci, Maria Alessandra PY - 2009 UR - https://vinar.vin.bg.ac.rs/handle/123456789/3700 AB - 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. T2 - Traffic T1 - 14-3-3 Ligand Prevents Nuclear Import of c-ABL Protein in Chronic Myeloid Leukemia VL - 10 IS - 6 SP - 637 EP - 647 DO - 10.1111/j.1600-0854.2009.00897.x ER -
@article{ author = "Mancini, Manuela and Veljković, Nevena V. and Corradi, Valentina and Zuffa, Elisa and Corrado, Patrizia and Pagnotta, Eleonora and Martinelli, Giovanni and Barbieri, Enza and Santucci, Maria Alessandra", year = "2009", 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.", journal = "Traffic", title = "14-3-3 Ligand Prevents Nuclear Import of c-ABL Protein in Chronic Myeloid Leukemia", volume = "10", number = "6", pages = "637-647", doi = "10.1111/j.1600-0854.2009.00897.x" }
Mancini, M., Veljković, N. V., Corradi, V., Zuffa, E., Corrado, P., Pagnotta, E., Martinelli, G., Barbieri, E.,& Santucci, M. A.. (2009). 14-3-3 Ligand Prevents Nuclear Import of c-ABL Protein in Chronic Myeloid Leukemia. in Traffic, 10(6), 637-647. https://doi.org/10.1111/j.1600-0854.2009.00897.x
Mancini M, Veljković NV, Corradi V, Zuffa E, Corrado P, Pagnotta E, Martinelli G, Barbieri E, Santucci MA. 14-3-3 Ligand Prevents Nuclear Import of c-ABL Protein in Chronic Myeloid Leukemia. in Traffic. 2009;10(6):637-647. doi:10.1111/j.1600-0854.2009.00897.x .
Mancini, Manuela, Veljković, Nevena V., Corradi, Valentina, Zuffa, Elisa, Corrado, Patrizia, Pagnotta, Eleonora, Martinelli, Giovanni, Barbieri, Enza, Santucci, Maria Alessandra, "14-3-3 Ligand Prevents Nuclear Import of c-ABL Protein in Chronic Myeloid Leukemia" in Traffic, 10, no. 6 (2009):637-647, https://doi.org/10.1111/j.1600-0854.2009.00897.x . .