PARENT SESSION
Implantation & Early Development

EXPRESSION OF INTERFERON IS REGULATED IS REGULATED BY PROTOONCOGENE c-jun AND CO-ACTIVATOR CBP.

Xu, Ningchun ¹, Matsuda, Fuko¹, Christenson, Ronald², Imakawa, Kazuhiko¹, Sakai, Senkiti¹, ^{1 2}

ABSTRACT- Regulation of interferon-tau (IFN) gene expression has been studied, however, the molecular mechanisms by which IFN gene is regulated have not been elucidated. In the present study, we investigated effects of co-activators, cAMP-response element binding protein (CREB)-binding protein (CBP) and p300, on ovine IFN (oIFN) gene activation in a transient transfection system using human choriocarcinoma JEG3 cells. The oIFN gene promoter/enhancer (-654 to +1 bases)-luciferase reporter construct (oIFN-pGL-3) was co-transfected with an expression construct of CBP (CBP/RSV) and/or p300 (pCMV-p300-HA). Levels of oIFN gene transactivation increased 1.9±0.2 and 3.0±0.4 fold when co-transfected with CBP and p300, respectively. These expressions further increased with a protein kinase C activator (PKC), phorbol 12-myristate 13-acetate (PMA) treatment, 4.7±0.7 and 3.7±0.5 fold, respectively. However, co-transfection of both CBP and p300 with or without PMA did not transactivate the oIFN construct beyond the level induced by the CBP plus PMA treatment. In addition, effects of protooncogenes, c-jun and c-fos, were examined by this transient transfection system. Transactivation of oIFN with c-jun was 3.5±0.6 and 2.9±0.3 fold with or without PMA, respectively, whereas c-fos did not affect its expression. Co-transfection of both c-jun and CBP resulted in 2.9±0.4 fold increase, which was further enhanced by PMA treatment (9.3±0.3 fold). These observations suggest that oIFN transactivation is regulated by c-jun and the effect is mediated through CBP.

KEY WORDS: IFN gene, CBP, c-jun, transcription