fig1

Figure 1. Schematic representation of the events leading to Notch signaling activation and the steps of this process affected by the oncogenic viruses simian virus 40 and human papillomavirus. Notch precursor is cleaved in the Golgi apparatus by a furin-like convertase and then exposed on the cell membrane. Notch ligands Delta/Jagged bind Notch extra-cellular subunit. This causes a disintegrin and metalloprotease to clip the extra-cellular portion of Notch transmembrane generating an intermediate, cleaved by γ-secretase which releases active Notch. Active Notch enters the nucleus, where it causes the dissociation of silencing mediator of retinoic acid and thyroid hormone receptor corepressor complex from C-promoter-binding factor 1/suppressor of hairless/Lag1, and recruits mastermind-like 1 coactivator complex, resulting in transcription of target genes. Simian virus 40 induces upregulation of the Notch pathway, whereas conflicting reports exist on the modulation of Notch by human papillomavirus (green arrow indicates up-regulation, red arrow indicates down-regulation or inhibitory binding)