Figure 3.
Pleiotropic activities of HDAC6 in protein quality control. Misfolded proteins accumulate upon cellular stress or proteasome inhibition. These ubiquitinated misfolded proteins are recognized by HDAC6 and displace basal interactors of HDAC, in particular Hsp90, HSF1 and VCP. Subsequently, client proteins can be released from Hsp90, HSF1 can trimerize and act as a transcription factor on HSE determined proteins, e.g. Hsp70. VCP exerts its segregase activity and helps in DSB repair upon cellular stress. HDAC6 targets misfolded proteins to the MTOC via microtubules and is also involved in the process of autophagy.