Hori Kazuya, Sen Anindya, Kirchhausen Tom, Artavanis-Tsakonas Spyros
Department of Cell Biology; Harvard Medical School; Boston, MA USA.
Commun Integr Biol. 2012 Jul 1;5(4):374-6. doi: 10.4161/cib.19995.
Notch signaling is an evolutionarily conserved mechanism that defines a key cell fate control mechanism in metazoans. Notch signaling relies on the surface interaction between the Notch receptor and membrane bound ligands in an apposing cell. In our recent study,(22) we uncover a non-canonical receptor activation path that relies on a ligand-independent, intracellular activation of the receptor as it travels through the endosomal compartments. We found that Notch receptor, targeted for degradation lysosomal degradation through multivesicular bodies (MVBs) is "diverted" toward activation upon mono-ubiquitination through a synergy between the ubiquitin ligase Deltex, the non-visual β-arrestin Kurtz and the ESCRT-III component Shrub. This activation path is not universal but appears to depend on the cellular context.
Notch信号通路是一种在进化上保守的机制，它定义了后生动物中一种关键的细胞命运控制机制。Notch信号通路依赖于Notch受体与相邻细胞中膜结合配体之间的表面相互作用。在我们最近的研究中，（22）我们发现了一种非经典的受体激活途径，该途径依赖于受体在通过内体区室时的配体非依赖性细胞内激活。我们发现，通过多泡体（MVBs）靶向溶酶体降解的Notch受体，在通过泛素连接酶Deltex、非视觉β-抑制蛋白Kurtz和ESCRT-III组分Shrub之间的协同作用进行单泛素化后，会“转向”激活。这种激活途径并非普遍存在，而是似乎取决于细胞环境。
