"Specifically, suberoylanilide hydroxamic acid (SAHA, also known as vorinostat), a FDA approved HDACi that inhibits class I, II, and IV HDACs, induces degradation of mutant p53 by inhibiting HDAC6 activity, an essential positive regulator of Hsp90, and subsequent disruption of the HDAC6/Hsp90/mutant p53 complex, leading to mutant p53 ubiquitination by MDM2 and CHIP."
"To further explore whether inhibitors of HSP90 and HDACs are capable of inducing Pirh2 expression to degrade mutant p53, HaCaT and MIA PaCa-2 cells were treated with 17AAG or SAHA."
"Vorinostat did not completely inhibit the mutant p53 population, and this was reflected in the estimated inhibitory coefficient for mutant p53 (I mp53 = 0.202 muM -1; Table 1)."
"cl.PARP.BCL-xL; BcL-xL (0) = 1 Vorinostat stimulates wild type p53 (wtp53) and inhibits mutant p53 (mp53) expression.10, 19, 20 In this study, p53 initially decreased, began to return to baseline around 24 hours, and eventually increased beyond the baseline."
"Importantly, we could demonstrate for the first time that the HDAC inhibitor SAHA is able to effectively and specifically downregulate mutant p53 protein by promoting its degradation, while having no effect on wild-type p53 protein levels (XREF_FIG)."
"Vorinostat sensitized DU145 cells to PARPi/IR and decreased mutant p53."
"It is known that SAHA induces the degradation of mutant p53 protein via inhibiting HDAC6, a member of class IIb HDACs."
"We found that mutant p53 protein was markedly decreased by ATO, 17AAG, or SAHA, and further decreased by combination of ATO with 17AAG or SAHA (XREF_FIG)."
"Wang et al. described that SAHA causes a massive reduction of mutant p53 through the disruption of the physical interaction between YY1 and HDAC8 [XREF_BIBR]."