Kidd S, Lieber T, Young M W
Laboratory of Genetics, The Rockefeller University, New York, New York 10021-6399 USA.
Genes Dev. 1998 Dec 1;12(23):3728-40. doi: 10.1101/gad.12.23.3728.
Notch, a transmembrane protein found in a wide range of organisms, is a component of a pathway that mediates cell-fate decisions that involve intercellular communication. In this paper, we show that in Drosophila melanogaster, Notch (N) is processed in a ligand-dependent fashion to generate phosphorylated, soluble intracellular derivatives. Suppressor of Hairless [Su(H)] is predominantly associated with soluble intracellular N. It has been demonstrated by others that N has access to the nucleus, and we show that when tethered directly to DNA, the cytoplasmic domain of N can activate transcription. Conversely, a viral activator fused to Su(H) can substitute for at least some N functions during embryogenesis. We suggest that one function of soluble forms of N is to bind to Su(H), and in the nucleus, to act directly as a transcriptional transactivator of the latter protein. Although N has functional nuclear localization signals, the N/Su(H) complex accumulates in the cytoplasm and on membranes suggesting that its nuclear entry is regulated. Localization studies in cultured cells and embryos suggest that Su(H) plays a role in this regulation, with the relative levels of Delta, N and Su(H) determining whether a N/Su(H) complex enters the nucleus.
Notch是一种在多种生物体中发现的跨膜蛋白，是介导涉及细胞间通讯的细胞命运决定途径的一个组成部分。在本文中，我们表明，在黑腹果蝇中，Notch（N）以配体依赖的方式进行加工，以产生磷酸化的可溶性细胞内衍生物。无毛抑制因子[Su(H)]主要与可溶性细胞内N相关。其他人已经证明N可以进入细胞核，并且我们表明，当直接与DNA相连时，N的细胞质结构域可以激活转录。相反，与Su(H)融合的病毒激活剂在胚胎发生过程中可以替代至少一些N的功能。我们认为，N的可溶性形式的一个功能是与Su(H)结合，并在细胞核中直接作为后者蛋白质的转录反式激活因子起作用。尽管N具有功能性核定位信号，但N/Su(H)复合物在细胞质和膜上积累，这表明其进入细胞核是受调控的。在培养细胞和胚胎中的定位研究表明，Su(H)在这种调控中起作用，Delta、N和Su(H)的相对水平决定了N/Su(H)复合物是否进入细胞核。
