c‐Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity‐dependent manner

c‐Abl is a non‐receptor‐type tyrosine kinase that regulates various cellular events, including cell proliferation, differentiation, and apoptosis, through phosphorylation of cytoplasmic and nuclear targets. Although we showed that c‐Abl induces histone deacetylation, the molecular mechanisms of this phenomenon are largely unknown. Here, we analyzed the effect of c‐Abl on the expression of histone deacetylase 1 (HDAC1), because c‐Abl was shown to be involved in maintenance of nuclear protein levels of HDAC1. Co‐transfection of HDAC1 with c‐Abl increased the levels of HDAC1 protein in a kinase activity‐dependent manner without affecting its mRNA levels. Treatment with the proteasome inhibitor MG132 increased protein levels of HDAC1 in cells transfected with HDAC1 but not in cells co‐transfected with HDAC1 and c‐Abl. Among class I HDACs, knockdown of endogenous c‐Abl preferentially suppressed endogenous protein levels of HDAC1, suggesting that c‐Abl stabilizes HDAC1 protein by inhibiting its proteasomal degradation. Subcellular fractionation showed that the stabilization of HDAC1 by c‐Abl occurred in the nucleus. Despite the fact that HDAC1 was phosphorylated by co‐expression with c‐Abl, stabilization of HDAC1 by c‐Abl was not affected by mutations in its sites phosphorylated by c‐Abl. Co‐expression with HDAC1 and nuclear‐targeted c‐Abl did not affect HDAC1 stabilization. Therefore, these results suggest that c‐Abl induces HDAC1 stabilization possibly through phosphorylation of a cytoplasmic target that is involved in proteasomal degradation of HDAC1.