Figure 5.

Scheme depicting our proposed Ras/NORE1A/β-TrCP/MDM2 senescence mechanism. The interaction of NORE1A to β-TrCP is Ras regulated, and this interaction regulates MDM2, a key negative regulator of p53 and Rb. Upon stimulation from Ras, MDM2 levels are suppressed by NORE1A and β-TrCP allowing levels of p53 and Rb to rise and activate an oncogene induced senescence mechanism. Accordingly, loss of NORE1A removes this key MDM2 regulatory mechanism, allowing for levels of MDM2 to increase resulting in excessive down-regulation of powerful tumor suppressive mechanisms operated by p53 and Rb.