Figure 1: A model on the regulation of nucleo-cytoplasmic shuttling and the functions of HDAC4. HDAC4 dynamically shuttles between nucleus and cytoplasm, depending on its phosphorylation status. Phosphorylated HDAC4 binds to 14-3-3 and remains in the cytoplasm. The cytoplasmic form of HDAC4 might possess protein deacetylase activity. Whether cytoplasmic HDAC4 possesses SUMO E3 ligase activity remains unclear. Dephosphorylated HDAC4 is imported into the nucleus, where reduction of HDAC4 by Trx1 favors nuclear retention. Oxidases that catalyze the reverse reaction remain to be identified. Nuclear HDAC4 possesses deacetylase as well as SUMO E3 ligase activities on substrates indicated in the figure.