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首页> 外文期刊>British Journal of Haematology >DNA hypermethylation promotes the low expression of pro-apoptotic BCL2L11 associated with BCR-ABL1 fusion gene of chronic myeloid leukaemia
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DNA hypermethylation promotes the low expression of pro-apoptotic BCL2L11 associated with BCR-ABL1 fusion gene of chronic myeloid leukaemia

机译:DNA高甲基化促进与慢性粒细胞白血病BCR-ABL1融合基因相关的促凋亡BCL2L11的低表达

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摘要

BCL2L11 [BCL2-interacting mediator, (BIM)] is a member of the BH3-only death activator family and a key determinant of cell fate upon cytokine withdrawal. Its expression is regulated by transcriptional and post-transcriptional mechanisms, encompassing the class O forkhead transcription factor-3A (FOXO3A), which directs gene transcription by binding a consensus site at the BCL2L11 promoter, and extracellular signal-regulated kinases (ERK1/2), which dissociate the most abundant BCL2L11EL isoform from pro-survival BCL2 proteins, concurrently targeting it for ubiquitylation and proteaso-mal degradation through phosphorylation at critical serine residues (Youle & Strasser, 2008). BCL2L11 downmodulation has a central role in the survival of clonal progenitors of chronic myeloid leukaemia (CML).
机译:BCL2L11 [BCL2相互作用介体(BIM)]是仅BH3死亡激活剂家族的成员,是细胞因子撤药后细胞命运的关键决定因素。它的表达受转录和转录后机制的调节,包括O类叉头转录因子3A(FOXO3A),它通过结合BCL2L11启动子的共有位点和细胞外信号调节激酶(ERK1 / 2)来指导基因转录。 ,可将最丰富的BCL2L11EL亚型与存活前的BCL2蛋白分离,并同时通过关键丝氨酸残基的磷酸化将其靶向进行泛素化和蛋白酶体降解(Youle&Strasser,2008)。 BCL2L11的下调在慢性粒细胞白血病(CML)的克隆祖细胞的存活中起着核心作用。

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