These stress signals also result in the activation of mouse double minute 2 homolog (MDM2), a protein that degrades p53.128 The p53 protein activates p21 that inhibits Cdk4/Cyclin D and Cdk2/Cyclin E complexes and prevents their cell cycle progression.129 Upon p53 activation the transcription of Cyclin B is also reduced, preventing cell cycle progression.130 Due to the importance of p53 in GBM pathogenesis, a gene therapy approach has been used to restore p53 expression. Here, TP53 is linked to glioblastoma.