Abstract
Fas-associated death domain (DD) adaptor (FADD), a member of the DD superfamily, contains both a DD and a death effector domain (DED) that are important in mediating FAS ligand-induced apoptotic signaling. P45 is a unique member of the DD superfamily in that it has a domain with sequence and structural characteristics of both DD and DED. We show that p45 forms a complex with FADD and diminishes Fas-FADD mediated death signaling. The DED of FADD is required for the complex formation with p45. Following spinal cord injury, transgenic mice over-expressing p45 exhibit increased neuronal survival, decreased retraction of corticospinal tract fibers and improved functional recovery. Understanding p45-mediated cellular and molecular mechanisms may provide insights into facilitating nerve regeneration in humans.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caspase 3 / metabolism
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Caspase 8 / metabolism
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Cell Death
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Cell Survival
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Enzyme Activation
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Fas Ligand Protein / metabolism
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Fas-Associated Death Domain Protein / chemistry
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Fas-Associated Death Domain Protein / metabolism*
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Female
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HEK293 Cells
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Humans
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Immunohistochemistry
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In Situ Nick-End Labeling
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Transgenic
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Neurons / metabolism*
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Neurons / pathology*
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Protein Structure, Tertiary
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Receptors, Death Domain / metabolism*
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Signal Transduction
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Spinal Cord Injuries / metabolism*
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Spinal Cord Injuries / pathology*
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Thy-1 Antigens / metabolism
Substances
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Fadd protein, mouse
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Fas Ligand Protein
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Fas-Associated Death Domain Protein
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Membrane Glycoproteins
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Nradd protein, mouse
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Receptors, Death Domain
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Thy-1 Antigens
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Caspase 3
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Caspase 8