cAMP応答性元素結合タンパク質（CREB）および活性化転写因子-1（ATF-1）による形質転換成長因子-BETA2プロモーターの転写調節は、プロテインキナーゼとコアクチベーターP300およびCREB結合タンパク質によって調節されます

形質転換成長因子-BETA2（TGF-BETA2）遺伝子の転写は、CREBとATF-1に結合したCAMP応答要素/アクティブ化転写因子（CRE/ATF）部位に依存し、上流の刺激因子1および2（USF1およびUSF2）に結合するE-Boxモチーフに依存しています。TGF-BETA2遺伝子の発現に関与する追加因子を特定するために、F9胚癌（EC）細胞を使用しました。転写因子の過剰発現、CREB、ATF-1、USF1、およびUSF2がF9分化細胞のTGF-BETA2プロモーター活性を劇的に増加させることを示しています。このリン酸化型は、親細胞と分化細胞の両方の全細胞抽出物に存在し、セリン133-リン酸化CREBの核蓄積がF9 EC細胞の分化中に調節され、TGF-BETA2遺伝子の活性化に重要な役割を果たす可能性が高いことを示唆しています。

Transcription of the transforming growth factor-beta2 (TGF-beta2) gene is dependent on a cAMP-response element/activating transcription factor (CRE/ATF) site that is bound by CREB and ATF-1 as well as an E-box motif that is bound by upstream stimulatory factors 1 and 2 (USF1 and USF2). To identify additional factors involved in the expression of the TGF-beta2 gene, we employed F9 embryonal carcinoma (EC) cells, which express TGF-beta2 only after the cells differentiate. We show that overexpression of the transcription factors, CREB, ATF-1, USF1, and USF2 dramatically increases TGF-beta2 promoter activity in F9-differentiated cells. We further show that the coactivators p300 and CBP up-regulate the TGF-beta2 promoter when CREB and ATF-1 are expressed in conjunction with protein kinases that phosphorylate CREB on serine 133 and ATF-1 on serine 63. Importantly, we identify the presence of serine 133-phosphorylated CREB in the nucleus of F9-differentiated cells but not in the nucleus of F9 EC cells. This phosphorylated form is present in whole cell extracts of both the parental and differentiated cells, suggesting that nuclear accumulation of serine 133-phosphorylated CREB is regulated during differentiation of F9 EC cells and is likely to play an important role in the activation of the TGF-beta2 gene.