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Cytoplasmatic compartmentalization by Bcr-Abl promotes TET2 loss-of-function in chronic myeloid leukemia
dc.creator | Mancini, Manuela | |
dc.creator | Veljković, Nevena V. | |
dc.creator | Leo, Elisa | |
dc.creator | Aluigi, Michela | |
dc.creator | Borsi, Enrica | |
dc.creator | Galloni, Chiara | |
dc.creator | Iacobucci, Ilaria | |
dc.creator | Barbieri, Enza | |
dc.creator | Santucci, Maria Alessandra | |
dc.date.accessioned | 2018-03-01T22:33:10Z | |
dc.date.available | 2018-03-01T22:33:10Z | |
dc.date.issued | 2012 | |
dc.identifier.issn | 0730-2312 | |
dc.identifier.uri | https://vinar.vin.bg.ac.rs/handle/123456789/4887 | |
dc.description.abstract | The loss-of-function of teneleven-translocation (TET) 2, a Fe2+-oxoglutarate-dependent dioxygenase catalyzing 5 methyl cytosine (5mC) conversion into 5-hydroxymethylcytosine (5hmC), contributes to the hematopoietic transformation in vivo. The aim of our study was to elucidate its role in the phenotype of chronic myeloid leukemia (CML), a myeloproliferative disease caused by the Bcr-Abl rearranged gene. We first confirmed TET2 interaction with the Bcr-Abl protein predicted by a Fourier-based bioinformatic method. Such interaction led to TET2 cytoplasmatic compartmentalization in a complex tethered by the fusion protein tyrosine kinase (TK) and encompassing the Forkhead box O3a (FoxO3a) transcription factor. We then focused the impact of TET2 loss-of-function on epigenetic transcriptional regulation of Bcl2-interacting mediator (BIM), a pro-apoptotic protein transcriptionally regulated by FoxO3a. BIM downregulation is a critical component of CML progenitor extended survival and is also involved in the disease resistance to imatinib (IM). Here we reported that TET2 release from Bcr-Abl protein following TK inhibition in response to IM triggers a chain of events including TET2 nuclear translocation, re-activation of its enzymatic function at 5mC and recruitment at the BIM promoter followed by BIM transcriptional induction. 5hmC increment following TET2 re-activation was associated with the reduction of histone H3 tri-methylation at lysine 9 (H3K9me3), which may contribute with DNA de-methylation reported elsewhere to recast a permissive epigenetic landscape for FoxO3a transcriptional activity. J. Cell. Biochem. 113: 27652774, 2012. (c) 2012 Wiley Periodicals, Inc. | en |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173001/RS// | |
dc.relation | Universita di Bologna (RFO), Ministero della Pubblica Istruzione, Universita e Ricerca (PRIN), Fondazione del Monte di Bologna e Ravenna, BolognaAIL, COST Action [BM0801], Fondazione Umberto Veronesi | |
dc.rights | restrictedAccess | en |
dc.source | Journal of Cellular Biochemistry | en |
dc.subject | CHRONIC MYELOID LEUKEMIA | en |
dc.subject | Bcr-Abl | en |
dc.subject | TET2 | en |
dc.subject | BIM | en |
dc.subject | FoxO3a | en |
dc.subject | EPIGENETIC MODIFICATIONS | en |
dc.title | Cytoplasmatic compartmentalization by Bcr-Abl promotes TET2 loss-of-function in chronic myeloid leukemia | en |
dc.type | article | en |
dcterms.abstract | Сантуцци, Мариа Aлессандра; Вељковић Невена В.; Манцини, Мануела; Лео, Елиса; Aлуиги, Мицхела; Борси, Енрица; Галлони, Цхиара; Иацобуцци, Илариа; Барбиери, Енза; | |
dc.citation.volume | 113 | |
dc.citation.issue | 8 | |
dc.citation.spage | 2765 | |
dc.citation.epage | 2774 | |
dc.identifier.wos | 000305334900024 | |
dc.identifier.doi | 10.1002/jcb.24154 | |
dc.citation.rank | M22 | |
dc.identifier.pmid | 22467095 | |
dc.identifier.scopus | 2-s2.0-84862517857 |
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