کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1997438 1065579 2009 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Baxβ: A Constitutively Active Human Bax Isoform that Is under Tight Regulatory Control by the Proteasomal Degradation Mechanism
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Baxβ: A Constitutively Active Human Bax Isoform that Is under Tight Regulatory Control by the Proteasomal Degradation Mechanism
چکیده انگلیسی

SummaryAlthough mRNAs of multiple isoforms of Bax, which encodes a central regulator of apoptosis signaling, have been reported, only Baxα protein has been well documented and studied. Baxα exists in latent form and is activated upon apoptosis induction through conformational changes. Here we demonstrate that Baxβ protein is ubiquitously present among human cells, but its activity is restricted through stringent regulation by proteasomal degradation. In contrast to Baxα, native Baxβ spontaneously integrates into mitochondrial membrane and is highly potent in inducing cytochrome c release from mitochondria. Remarkably, Baxβ protein is upregulated by apoptotic stimuli via inhibition of its ubiquitination process, and stable expression of Baxβ in HCT116-Bax−/− cells restores their sensitivity to multiple stimuli. Baxβ associates with and promotes Baxα activation. Moreover, selective knockdown of Baxβ desensitizes HCT116-Bax+/− cells to Bax-dependent apoptosis signaling. These observations underscore the plasticity of human Bax in serving its role as a “gatekeeper” for apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 33, Issue 1, 16 January 2009, Pages 15–29
نویسندگان
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