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

作者：Li, Qingjie^*; Luo, Cunhui; Loehr, Christiane V.; Dashwood, Roderick H.

来源：Hepatology Research, 2011, 41(8): 776-783.

DOI：10.1111/j.1872-034X.2011.00827.x

• activator protein-1
• activator protein AP-2
• GATA4 transcription factor
• liver
• protein kinase A

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

• 出版日期2011-8
• 单位湖南农业大学; 湖南省药品检验所