P45 forms a complex with FADD and promotes neuronal cell survival following spinal cord injury.
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.
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California, United States of America.
Tsung-Chang
TC
Sung
Zhijiang
Z
Chen
Sandrine
S
Thuret
Marçal
M
Vilar
Fred H
FH
Gage
Roland
R
Riek
Kuo-Fen
KF
Lee
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D017434:Protein Structure, Tertiary; D053218:Receptors, Death Domain / Q000378:metabolism*; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D018800:Thy-1 Antigens / Q000378:metabolism
C505534:Fadd protein, mouse; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D008562:Membrane Glycoproteins; C480683:Nradd protein, mouse; D053218:Receptors, Death Domain; D018800:Thy-1 Antigens; D053148:Caspase 3; D053181:Caspase 8