Histone deacetylases (HDACs) play important roles in fundamental cellular 
processes, and HDAC inhibitors are emerging as promising cancer therapeutics. 
p73, a member of the p53 family, plays a critical role in tumor suppression and 
neural development. Interestingly, p73 produces two classes of proteins with 
opposing functions: the full-length TAp73 and the N-terminally truncated ΔNp73. 
In the current study, we sought to characterize the potential regulation of p73 
by HDACs and found that histone deacetylase 1 (HDAC1) is a key regulator of 
TAp73 protein stability. Specifically, we showed that HDAC1 inhibition by HDAC 
inhibitors or by siRNA shortened the half-life of TAp73 protein and subsequently 
decreased TAp73 expression under normal and DNA damage-induced conditions. 
Mechanistically, we found that HDAC1 knockdown resulted in hyperacetylation and 
inactivation of heat shock protein 90, which disrupted the interaction between 
heat shock protein 90 and TAp73 and thus promoted the proteasomal degradation of 
TAp73. Functionally, we found that down-regulation of TAp73 was required for the 
enhanced cell migration mediated by HDAC1 knockdown. Together, we uncover a 
novel regulation of TAp73 protein stability by HDAC1-heat shock protein 90 
chaperone complex, and our data suggest that TAp73 is a critical downstream 
mediator of HDAC1-regulated cell migration.