Fig. 7. Schematic representation of the mechanism of HDAC2 degradation. Proteasomal degradation of HDAC2 involves the E3 ubiquitin ligase RLIM and in untreated cells is limited by the abundance of an E2 ubiquitin conjugase, presumably Ubc8. We cannot exclude the involvement of additional E2 and E3 enzymes. In VPA-treated cells, Ubc8 is induced and the degradation of HDAC2 is enhanced. In TSA-treated cells, the amount of RLIM is reduced in addition to induction of Ubc8. Under these conditions, the abundance of the ubiquitin ligase RLIM limits the rate of HDAC2 degradation to a level similar to that in untreated cells.