کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1928897 1050430 2013 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Neddylation pathway regulates the proliferation and survival of macrophages
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Neddylation pathway regulates the proliferation and survival of macrophages
چکیده انگلیسی

Neddylation is a new type of protein post-translational modification which adds the ubiquitin-like molecule Nedd8 to target proteins. The well-identified targets of neddylation are cullins, which serve as essential components of Cullin-RING E3 ligases (CRL). It is reported that inhibition of neddylation repressed NF-κB-mediated proinflammatory cytokine production in macrophages. However, the role of neddylation in the proliferation and survival of macrophages has not been well defined. Here we report that partial inactivation of the neddylation pathway by a specific Nedd8-activating enzyme E1 (NAE) inhibitor MLN4924 reduced LPS-induced production of the proinflammatory cytokines TNF-α and IL-6 without obvious impairment of cell viability. However, persistent and severe inactivation of neddylation by MLN4924 significantly inhibited cell proliferation by inducing G2 phase cell-cycle arrest and further triggered cell death by inducing apoptosis in RAW264.7 macrophages. Mechanistic analysis revealed that inactivation of neddylation blocked cullin neddylation, inhibited CRL E3 ligase activity, and thus led to the accumulation of CRL substrates, resulting in cell-cycle arrest, DNA damage response and apoptosis. The findings revealed that neddylation serves as an important signaling pathway regulating the proliferation and survival of macrophages.


► Partial inactivation of neddylation does not impairs macrophage viability.
► Partial inactivation of neddylation inhibits the function of macrophages.
► Persistent inactivation of neddylation induces G2 phase arrest in macrophages.
► Persistent inactivation of neddylation triggers apoptosis.
► Neddylation pathway is critical for macrophage proliferation and survival.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 432, Issue 3, 15 March 2013, Pages 494–498
نویسندگان
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