Arbiter of differentiation and death: Notch signaling meets apoptosis

Abstract

Notch-ligand interactions are a highly conserved mechanism that regulates cell fate decisions. Over the past few years, numerous observations have shown that this mechanism operates to regulate cell differentiation in an enormous variety of developmental and cell maturation processes. Recent studies indicate that in addition to cell differentiation, Notch signaling has direct effects on proliferation and programmed cell death. The picture emerging from these findings suggests that, depending on cellular and developmental context, Notch signaling may function as a general "arbiter" of cell fate, regulating differentiation potential, rate of proliferation, and apoptotic cell death. In this review, we briefly summarize the current knowledge of the structure and function of Notch receptors and discuss the recent evidence that Notch signaling regulates apoptotic cell death. The possible mechanisms of this effect and its potential implications for developmental biology, immunobiology, neuropathology, and tumor biology are discussed.

Retracted: Down‐regulation of Jagged‐1 induces cell growth inhibition and S phase arrest in prostate cancer cells

“…Alteration of these functions in the adult has been associated with various types of cancer in which Notch may act as an oncogene with certain exception. 6,7 Jagged-1, a Notch receptor ligand, is highly expressed in prostate cancer cells. 8,9 It was found to be increased in the conditioned media in prostate cancer cells.…”

Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1

“…19 We thus examined the effects of Notch1 signaling on apoptosis resistance in glioblastoma cells. The knockdown of Notch1 induced apoptosis in 15 to 20% of U251MG cells and 20 to 30% of U373MG cells, but had no apoptosis-inducing effect in U87MG, LN229, NCH89 and NCH468 cells (Supplementary Figure S1).…”

Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2

“…5 Expression of CD23a has been implicated in cell survival in B-CLL cells, 4 and Notch proteins were shown to inhibit apoptosis in several models. [17][18][19]46,47 To investigate the effect of PI on Notch2 activity and CD23 expression, two compounds, bortezomib, which has already been employed in clinical trials for several malignancies, 33,34,48,49 and MG-132 were tested. Bortezomib and MG-132 efficiently induced apoptosis in B-CLL cells in vitro and this process was accompanied by a decrease in the expression of CD23.…”

“…14,15 Importantly, activation of Notch proteins has been demonstrated to inhibit apoptosis in different cellular contexts. [16][17][18][19][20] Notch1 expression provides significant protection to thymocytes and T-cell lines from glucocorticoid and TCRmediated apoptosis, respectively. 16,17 Protective function for Notch1 has further been described for murine erythroleukemia cells by controlling the apoptotic threshold during differentiation and growth.…”