Activator protein-2 functions as a master regulator of multiple transcription factors in the mouse liver.
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AIM: Activator protein 2 (AP-2) 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-2 in hepatocytes is unknown. The present study is to characterize the expression and function of AP-2 in the liver of conscience mouse. METHODS: Exogenous AP-2 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-2 is expressed in the nuclei of mouse hepatocytes. Overexpression of AP-2in 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-3 and PKA, which regulates the phosphorylation status and stability of GATA-4 protein. CONCLUSIONS: AP-2 is expressed in mouse hepatocytes and it acts as a master regulator of numerous transcription factors in the liver.
