Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California, United States of America.
PLoS One. 2013 Jul 23;8(7):e69286. doi: 10.1371/journal.pone.0069286. Print 2013.
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.
Fas 相关死亡结构域（DD）衔接蛋白（FADD）是 DD 超家族的成员，它包含一个 DD 和一个死亡效应结构域（DED），在介导 Fas 配体诱导的凋亡信号中起着重要作用。P45 是 DD 超家族的一个独特成员，因为它具有一个具有 DD 和 DED 序列和结构特征的结构域。我们发现 p45 与 FADD 形成复合物，并减弱 Fas-FADD 介导的死亡信号。FADD 的 DED 对于与 p45 的复合物形成是必需的。在脊髓损伤后，过表达 p45 的转基因小鼠表现出神经元存活增加、皮质脊髓束纤维回缩减少和功能恢复改善。了解 p45 介导的细胞和分子机制可能为促进人类神经再生提供思路。
