Activator protein-2α functions as a master regulator of multiple transcription factors in the mouse liver

Aim: Activator protein 2α (AP‐2α) belongs to the AP‐2 family of transcription factors that are involved in the regulation of cell proliferation, differentiation, apoptosis and carcinogenesis and has been suggested to function as a tumor suppressor in many cancers. However, the physiological role of AP‐2α in hepatocytes is unknown. The present study is to characterize the expression and function of AP‐2α in the liver of conscience mouse. Methods: Exogenous AP‐2α was overexpressed in the mouse liver by in vivo gene delivery and changes in transcription factor expression were identified by using protein‐DNA arrays and immunoblotting. Results: Western blotting and protein/DNA arrays showed that AP‐2α is expressed in the nuclei of mouse hepatocytes. Overexpression of AP‐2αin vivo significantly suppressed transcription factors AP‐1, CREB and c‐Myc, and markedly increased CBF, c‐Myb, NF‐1, Pax‐5, RXR, Smad3/4, TR(DR‐4), USF‐1 and GATA. Among all GATA proteins, only GATA‐4 level was dramatically elevated and there was a concomitant loss of phospho‐GATA‐4. Corresponding changes were detected in upstream kinases Akt, GSK‐3β and PKA, which regulates the phosphorylation status and stability of GATA‐4 protein. Conclusions: AP‐2α is expressed in mouse hepatocytes and it acts as a master regulator of numerous transcription factors in the liver.