Figure 2.

Pathways of cellular senescence. Due to cellular stressors like telomere shortening, DNA damage, oxidative stress and the expression of oncogenes, senescence genes are induced. The TP53 gene encodes for P53, which induces P21, a cyclin dependent kinase inhibitor (CDK) blocking CDK4/6. As a result, phosphorylation of the retinoblastoma protein (pRB) is hindered. Consequently, the cell cannot enter the S-phase and the cell cycle is arrested in the G1 phase. The INK4a/ARF locus encodes for P14^ARF and P16^INK4a protein. P14^ARF is a regulator of P53 activity: by binding mouse double minute 2 homolog (MDM2), degradation of p53 is avoided. Like P53, P16^INK4a represses CDK4/6 by which pRB is not phosphorylated and cell cycle progression is prohibited. Figure adapted from [32].