Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
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Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
The receptor-interacting serine-threonine kinase 3 (RIP3) is a key signaling molecule in the programmed necrosis (necroptosis) pathway. This pathway plays important roles in a variety of physiological and pathological conditions, including development, tissue damage response, and antiviral immunity. Here, we report the identification of a small molecule called (E)-N-(4-(N-(3-methoxypyrazin-2-yl...
متن کاملMixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3.
Programmed necrotic cell death induced by the tumor necrosis factor alpha (TNF-α) family of cytokines is dependent on a kinase cascade consisting of receptor-interacting kinases RIP1 and RIP3. How these kinase activities cause cells to die by necrosis is not known. The mixed lineage kinase domain-like protein MLKL is a functional RIP3 substrate that binds to RIP3 through its kinase-like domain ...
متن کاملMixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis.
Tumor necrosis factor (TNF) is an important inflammatory cytokine and induces many cellular responses, including inflammation, cell proliferation, apoptosis, and necrosis. It is known that receptor interacting protein (RIP) kinases, RIP1 and RIP3, are key effectors of TNF-induced necrosis, but little is known about how these two RIP kinases mediate this process, although reactive oxygen species...
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Background: MLKL, one of the main downstream components of the necroptosis or programmed necrosis has recently been demonstrated in advanced atherosclerotic lesions. However, its precise role in the atherosclerosis pathogenesis still requires more elucidation. Our study was set to delineate both the changes in peripheral MLKL gene expression and its influence on disease severity in atherosclero...
متن کاملThe degradation of mixed lineage kinase domain-like protein promotes neuroprotection after ischemic brain injury
Mixed lineage kinase domain-like (MLKL) protein was recently found to play a critical role in necrotic cell death. To explore its role in neurological diseases, we measured MLKL protein expression after ischemia injury in a mouse model. We found that MLKL expression significantly increased 12 h after ischemia/reperfusion (I/R) injury with peak levels at 48 h. Inhibition of MLKL by intraperitone...
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ژورنال
عنوان ژورنال: Cell
سال: 2012
ISSN: 0092-8674
DOI: 10.1016/j.cell.2011.11.031