TY - JOUR
T1 - Activator protein-2α functions as a master regulator of multiple transcription factors in the mouse liver
AU - Li, Qingjie
AU - Luo, Cunhui
AU - Löhr, Christiane V.
AU - Dashwood, Roderick H.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Activator protein AP-2
KW - Activator protein-1
KW - GATA4 transcription factor
KW - Liver
KW - Protein kinase A
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U2 - 10.1111/j.1872-034X.2011.00827.x
DO - 10.1111/j.1872-034X.2011.00827.x
M3 - Article
C2 - 21682828
AN - SCOPUS:79960742247
SN - 1386-6346
VL - 41
SP - 776
EP - 783
JO - Hepatology Research
JF - Hepatology Research
IS - 8
ER -