The role of human ADA2a in the regulation of p53 acetylation and stability

Abstract

The tumor suppressor protein p53 is a well-known transcription factor that functions as a critical component of the genotoxic stress response via regulating the expression of effector proteins that control cellular fate following DNA damage. The human p300/CBP-associated factor (PCAF)-containing histone acetyltransferase (HAT) complex is important for the stability and activity of p53 via its acetylation. The human homolog of yeast alteration/deficiency in activation 2a (ADA2a) is a stable component of the human PCAF-containing HAT complex. In this study, we demonstrated that p53 and hADA2a physically interact with each other in human HEK 293T cells. Using overexpression and small interfering RNA-mediated knockdown, we demonstrated that hADA2a stabilizes p53 via promoting its acetylation at lysine 320 -a PCAF-dependent acetylation site. Furthermore, hADA2a can potentiate the transcriptional activity of p53 at the BAX and p21 promoters to induce cell apoptosis and cell cycle arrest. Overall, our results establish that hADA2a, a component of the PCAF-containing histone acetyltransferase co-activator complex, is a mediator of acetylation-dependent stabilization and activation of p53 in mammalian cells. hADA2a, p53, acetylation, PCAF Citation:Huang J, Zhang L, Xiao L, et al. The role of human ADA2a in the regulation of p53 acetylation and stability.

α-Synuclein A53T Binds to Transcriptional Adapter 2-Alpha and Blocks Histone H3 Acetylation

“…TADA2a has been studied as a key component of the PCAF and Ada two-A-containing (ATAC) HAT complexes [30] contributing to histone and non-histone acetylation. For example, TADA2a interacts with p53 to promote the acetylation of p53 at lysine 320, increasing its stability and activity [17,31]. TADA2a may also impact acetylation in a variety of ways during DNA damage-induced apoptosis and cell-cycle arrest [17].…”

CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest

“…The pcDB-CCDC134-myc/his and hADA2a-GFP plasmids had been described previously (Huang et al 2011). CCDC134 siRNA and control siRNA were synthesized by GeneChem Corporation (Shanghai, China), and the sequences of the various siRNA had been reported previously (Huang et al 2008).…”