Fig. 6

Schematic representation of p73 involvement in the regulation of senescence. In blue, molecules that promote and in orange—molecules that repress senescence. TAp73 inhibits TERT activity, however, the effect on senescence is not established [329]. In contrast, DNp73 represses p53/p73 activating signalling emanating from the DNA double stranded breaks by the ATM/ATR signalling also repressing senescence [52]. TAp73 induced transcription of the mitochondrial enzymes Cox4i1 regulating ROS, ATP levels and oxygen consumption is critical for senescence repression in MEFs [87]. Similarly p73 target genes GLS2 is a key enzyme in glutathione biosynthesis to reduce ROS level [330, 331] and FDXR has roles in electron transfer to p450 and p73 mRNA stability by IRP2 regulation [332]. Altogether, these processes lead to higher oxidation rate and ATP generation, glutathione biosynthesis, lower ROS levels and inhibition of senescence