Fig. 8. Working hypothesis.

The diagram shows the working hypothesis based on the present work and the previously established mechanisms to regulate HDAC2 activity in the development of cardiac hypertrophy. HDAC2, a class-I HDAC⁴⁹, and its posttranslational modification play an important role in the development of cardiac hypertrophy. In the basal state, HDAC2 is kept unphosphorylated and deacetylated by its association with PP2A and HDAC5, respectively (present work). In the activated state induced by hypertrophic stimuli, HDAC5 is then phosphorylated and shuttles out from the nucleus¹³. Simultaneously, pCAF interacts with HDAC2 to induce its acetylation¹⁷. After the acetylation of HDAC2, hypertrophic stresses further induce both the dissociation of PP2A (present work) and cytosol-to-nuclear relocalization of CK2α1¹⁶, which simultaneously result in the phosphorylation of HDAC2 S394. For ease of understanding, the hypertrophy non-responsive basal phosphorylation of HDAC2 is not included in the present diagram. Abbreviations: Ac, acetylation. P, phosphorylation