Program in Molecular and Cellular Biology, University of Massachusetts , Amherst, MA , USA.
Program in Molecular and Cellular Biology, University of Massachusetts , Amherst, MA , USA ; Department of Veterinary and Animal Sciences, University of Massachusetts , Amherst, MA , USA.
Front Oncol. 2014 Dec 4;4:345. doi: 10.3389/fonc.2014.00345. eCollection 2014.
Canonical Notch signaling is initiated by γ-secretase-mediated cleavage of the Notch receptor, leading to the release of the active intra-cellular domain of Notch that migrates to the nucleus and interacts with RBP-Jκ, resulting in the activation of downstream target genes. While canonical Notch signaling is well known to play an active role in several steps during development as well in multiple cell fate decisions, recent evidence from both invertebrate and vertebrate systems indicates that non-canonical, RBP-Jκ-independent signaling is important in several cellular processes including oncogenesis and activation of T lymphocytes. These observations raise the possibility that, through an understanding of non-canonical Notch signaling, novel strategies for inhibiting Notch signaling may prove useful in the design of therapies targeted to block aberrant Notch activity. In this mini-review, we will examine the current data demonstrating a non-canonical role for Notch signaling in both cancer and the immune system and suggest a better understanding of non-canonical signaling may reveal novel strategies to block Notch signaling in disease.
经典的 Notch 信号通路是由 γ-分泌酶介导的 Notch 受体切割起始的，导致 Notch 的活性胞内结构域释放，迁移到细胞核并与 RBP-Jκ 相互作用，从而激活下游靶基因。虽然经典的 Notch 信号通路在发育过程中的几个步骤以及多个细胞命运决定中起着积极的作用，但来自无脊椎动物和脊椎动物系统的最新证据表明，非经典的、不依赖于 RBP-Jκ 的信号通路在包括肿瘤发生和 T 淋巴细胞激活在内的几个细胞过程中是重要的。这些观察结果提出了一种可能性，即通过对非经典 Notch 信号通路的理解，抑制 Notch 信号通路的新策略可能有助于设计针对阻断异常 Notch 活性的治疗方法。在这篇简短的综述中，我们将检查目前的数据，这些数据表明 Notch 信号在癌症和免疫系统中具有非经典的作用，并提出对非经典信号通路的更好理解可能会揭示出在疾病中阻断 Notch 信号通路的新策略。
