کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8434257 1546637 2018 57 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ABT-263-induced MCL1 upregulation depends on autophagy-mediated 4EBP1 downregulation in human leukemia cells
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
ABT-263-induced MCL1 upregulation depends on autophagy-mediated 4EBP1 downregulation in human leukemia cells
چکیده انگلیسی
The present study aimed to investigate the pathway related to MCL1 expression in ABT-263-treated human leukemia U937 cells. ABT-263 upregulated MCL1 protein expression but did not affect its mRNA level and protein stability. Notably, ABT-263 increased 4EBP1 mRNA decay and thus reduced 4EBP1 expression. Overexpression of 4EBP1 abrogated ABT-263-induced MCL1 upregulation. ABT-263-induced activation of IKKα/β-NFκB axis elicited autophagy of U937 cells, leading to reduced mRNA stability of 4EBP1. Inhibition of the IKKα/β-NFκB axis or autophagy mitigated the effect of ABT-263 on 4EBP1 and MCL1 expression. Amsacrine enhanced the cytotoxicity of ABT-263 in human leukemia U937, HL-60, and Jurkat cells because of its inhibitory effect on the IKKα/β-NFκB-mediated pathway. Our data indicate that ABT-263 alleviates the inhibitory effect of 4EBP1 on MCL1 protein synthesis through IKKα/β-NFκB-mediated induction of autophagy, and suggest a promising strategy to improve anti-leukemia therapy with ABT-263.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 432, 28 September 2018, Pages 191-204
نویسندگان
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