Teng Huajian, Ballim Reyna Deeya, Mowla Shaheen, Prince Sharon
Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925 Cape Town, South Africa.
J Biol Chem. 2009 Sep 25;284(39):26368-76. doi: 10.1074/jbc.M109.021360. Epub 2009 Jul 24.
The mechanism(s) regulating the expression of the TBX2 gene, a key regulator of development, is poorly understood and thus limits an understanding of its function(s). Here we demonstrate that 12-O-tetradecanoylphorbol-13-acetate (TPA) induces TBX2 expression in normal human fibroblasts in a protein kinase C (PKC)-dependent and MAPK-independent manner. Our data further reveal that TPA activates transcription of TBX2 through activating MSK1, which leads to an increase in phosphorylated histone H3 and the recruitment of Sp1 to the TBX2 gene. In addition, TPA was shown to activate MSK1 in a PKC-dependent and MAPK-independent manner. This study is the first to provide evidence that phosphorylation of histone H3 leads to the transcriptional activation of the TBX2 gene and to link MSK1 to PKC.
TBX2基因是发育的关键调节因子，但其调控机制尚不清楚，这限制了人们对其功能的理解。在此，我们证明12-O-十四烷酰佛波醇-13-乙酸酯（TPA）以蛋白激酶C（PKC）依赖且丝裂原活化蛋白激酶（MAPK）非依赖的方式诱导正常人成纤维细胞中TBX2的表达。我们的数据进一步表明，TPA通过激活MSK1来激活TBX2的转录，这导致磷酸化组蛋白H3增加以及Sp1募集到TBX2基因。此外，TPA被证明以PKC依赖且MAPK非依赖的方式激活MSK1。本研究首次提供证据表明组蛋白H3的磷酸化导致TBX2基因的转录激活，并将MSK1与PKC联系起来。
