Abstract
The tumor suppressor p53 is a transcriptional regulator that controls expression of its target genes involved in cell cycle arrest, apoptosis in response to various kinds of stress including DNA damage. The most famous p53 target gene is the cyclin-dependent kinase inhibitor p21, the principal mediator of p53-induced cell cycle arrest. A switch to an apoptotic responses lead an induction of p53-mediated apoptotic target genes like Bax and Puma.
The spindle checkpoint is a guardian of genome instabilities. Mad2 is a key player in the spindle checkpoint mechanism. p31comet serves as a silencer of Mad2-dependent spindle checkpoint.
Here, we report an additional role of p31comet in control of p53. p31comet binds to p53 and p31comet-depleted cells sensitized against DNA damage reagents and undergo p53-dependent apoptosis. Although p53 can induce apoptotic target genes under depletion of p31comet, p53-mediated p21 induction is diminished. Upon depletion of p31comet, p53 becomes highly acetylated at Lys120 within the DNA-binding domain of p53, which is catalyzed by Histone acetylase TIP60. Introduction of site-specific mutantion at Lys 120 residue can suppress apoptosis in p31comet -depleted cells with DNA damage. p31comet appears to determine the cell fate, death or survival, by controlling p53 through acetylation.
