BMP2-activated Erk / MAP激酶稳定Runx2通过增加p300和组蛋白乙酰转移酶的活动水平。
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小君JH, Yoon WJ Seo某人,吸引公里,金GS, Ryoo嗯,门敏JH
BMP2-activated Erk / MAP激酶稳定Runx2通过增加p300和组蛋白乙酰转移酶的活动水平。
J生物化学杂志。2010年11月19日,285 (47):36410 - 9。doi: 10.1074 / jbc.M110.142307。Epub 2010年9月17日。
- PubMed ID
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20851880 (在PubMed]
- 文摘
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Runx2是成骨细胞分化的关键转录因子。监管Runx2表达水平和转录活动对全身的骨形成蛋白(BMP)是重要的成骨细胞分化。之前的研究表明,细胞外signal-regulated激酶(Erk)激活增强Runx2的转录活动,BMP-induced Runx2乙酰化作用增加Runx2稳定和转录活动。因为BMP信号诱导成骨细胞Erk激活,我们试图调查是否BMP-induced Erk信号调节Runx2乙酰化和稳定性。Erk激活的超表达持续活跃MEK1 Runx2转录活动增加,而U0126 MEK1/2的抑制剂,抑制基底Runx2转录活性和BMP-induced Runx2乙酰化作用和稳定。超表达持续活跃的MEK1稳定Runx2通过上调的乙酰化和下调泛素化的蛋白质。Erk激活p300增加蛋白质含量和组蛋白乙酰转移酶的活动。击倒的p300用siRNA减少Erk-induced Runx2稳定。超表达Smad5增加Runx2乙酰化作用和稳定。Erk激活进一步增加Smad-induced Runx2乙酰化作用和稳定,而U0126镇压这些函数。 On the other hand, knockdown of Smad1 and Smad5 by siRNA suppressed both basal and Erk-induced Runx2 protein levels. Erk activation enhanced the association of Runx2 with p300 and Smad1. Taken together these results indicate that Erk signaling increases Runx2 stability and transcriptional activity, partly via increasing p300 protein levels and histone acetyltransferase activity and subsequently increasing Runx2 acetylation by p300. In addition to the canonical Smad pathway, a BMP-induced non-Smad Erk signaling pathway cooperatively regulates osteoblast differentiation partly via increasing the stability and transcriptional activity of Runx2.