Tcherpakov Marianna, Bronfman Francisca C, Conticello Silvestro G, Vaskovsky Anna, Levy Zehava, Niinobe Michio, Yoshikawa Kazuaki, Arenas Ernest, Fainzilber Mike
Molecular Neurobiology Group, Department of Biological Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel.
J Biol Chem. 2002 Dec 20;277(51):49101-4. doi: 10.1074/jbc.C200533200. Epub 2002 Oct 31.
The p75 neurotrophin receptor has been implicated in diverse aspects of neurotrophin signaling, but the mechanisms by which its effects are mediated are not well understood. Here we identify two MAGE proteins, necdin and MAGE-H1, as interactors for the intracellular domain of p75 and show that the interaction is enhanced by ligand stimulation. PC12 cells transfected with necdin or MAGE-H1 exhibit accelerated differentiation in response to nerve growth factor. Expression of these two MAGE proteins is predominantly cytoplasmic in PC12 cells, and necdin was found to be capable of homodimerization, suggesting that it may act as a cytoplasmic adaptor to recruit a signaling complex to p75. These findings indicate that diverse MAGE family members can interact with the p75 receptor and highlight type II MAGE proteins as a potential family of interactors for signaling proteins containing type II death domains.
p75神经营养因子受体参与了神经营养因子信号传导的多个方面，但其介导作用的机制尚未完全明确。在此，我们鉴定出两种黑色素瘤相关抗原（MAGE）蛋白，即necdin和MAGE-H1，它们是p75细胞内结构域的相互作用蛋白，并且发现配体刺激可增强这种相互作用。用necdin或MAGE-H1转染的PC12细胞对神经生长因子的反应表现出加速分化。这两种MAGE蛋白在PC12细胞中的表达主要位于细胞质中，并且发现necdin能够形成同源二聚体，这表明它可能作为一种细胞质衔接蛋白，将信号复合物招募至p75。这些发现表明，不同的MAGE家族成员可与p75受体相互作用，并突出了II型MAGE蛋白作为含有II型死亡结构域的信号蛋白潜在相互作用蛋白家族的地位。
