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P45 forms a complex with FADD and promotes neuronal cell survival following spinal cord injury.

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.

SUBMITTER: Sung TC

PROVIDER: S-EPMC3720591 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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P45 forms a complex with FADD and promotes neuronal cell survival following spinal cord injury.

Sung Tsung-Chang TC Chen Zhijiang Z Thuret Sandrine S Vilar Marçal M Gage Fred H FH Riek Roland R Lee Kuo-Fen KF

PloS one 20130723 7

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. Fol ...[more]

PMID: 23935974

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