Induction of Cyclin D1 Transcription and CDK2 Activity by Notch^ic: Implication for Cell Cycle Disruption in Transformation by Notch^ic

Abstract

Notch genes encode a family of transmembrane proteins that are involved in many cellular processes such as differentiation, proliferation, and apoptosis. Although it is well established that all four Notch genes can act as oncogenes, the mechanism by which Notch proteins transform cells remains unknown.

siRNA-mediated Silencing of Notch-1 Enhances Docetaxel Induced Mitotic Arrest and Apoptosis in PCa Cells

“…Furthermore, p21 waf1/cip1 is an important transcriptional target of p53 and mediates DNA damageinduced cell-cycle arrest in G 1 and G 2 (el-Deiry et al, 1993). Thus, p21 waf1/cip1 could contribute to S phase arrest following Notch-1 knockdown in PC-3 cells, consistent with the report that p21 waf1/cip1 plays an important role in controlling prostate cancer growth (Ronchini and Capobianco, 2001). …”

Notch Signaling and Schwann Cell Transformation: Development of a Model System and Application to Human MPNSTs

“…The CyclinD1 promoter has been proposed to be a direct target of NICD (6). Although this is not consistent with our data concerning the down-regulation of CyclinD1 by ligand-induced signaling (see 2005 report), we considered the possibility that high concentrations of NICD might be able to transcriptionally activate CyclinD1.…”

The Notch signaling pathway: Transcriptional regulation at Notch target genes

“…Two other Notch target genes, NRARP and Deltex-1 were shown to be potent negative regulators of Notch signaling [23,24]. Furthermore, Notch target genes implicated in cancer are c-myc [16,25,26], cyclinD1 [27] and p21/Waf1 [28]. Other Notch target genes are NFkB2 [29], Ifi-202, Ifi-204, Ifi-D3, and ADAM19 [19].…”