中科院上海生命科學(xué)院,、上海交通大學(xué)醫(yī)學(xué)院健康科學(xué)研究所的研究人員發(fā)現(xiàn)了酪氨酸蛋白激酶Btk轉(zhuǎn)錄調(diào)節(jié)的新機(jī)制：組蛋白乙酰轉(zhuǎn)移酶p300介導(dǎo)的組蛋白乙酰化正調(diào),，而組蛋白去乙?；?介導(dǎo)的組蛋白去乙酰化負(fù)調(diào)Btk轉(zhuǎn)錄及表達(dá),。這些結(jié)果拓展了對Btk調(diào)節(jié)及其功能的認(rèn)識,，并有益于對相關(guān)疾病的研究。
這一研究成果公布在美國免疫學(xué)會會刊《免疫學(xué)雜志》(Journal of Immunology)上,，領(lǐng)導(dǎo)這一研究的是上海交通大學(xué)醫(yī)學(xué)院上海市免疫研究所研究員孫健博士,，其早年畢業(yè)于遵義醫(yī)學(xué)院，曾發(fā)現(xiàn)并鑒定了一種新的系統(tǒng)性紅斑狼瘡單基因缺失小鼠模型---轉(zhuǎn)錄因子Aiolos基因敲除小鼠,。
酪氨酸蛋白激酶Btk在B細(xì)胞受體信號傳導(dǎo)中起重要作用,。Btk基因突變導(dǎo)致人與小鼠發(fā)生免疫缺陷。該項研究揭示了Btk轉(zhuǎn)錄調(diào)節(jié)的新機(jī)制—組蛋白乙酰轉(zhuǎn)移酶p300介導(dǎo)的組蛋白乙?；{(diào),，而組蛋白去乙酰化酶1介導(dǎo)的組蛋白去乙?；?fù)調(diào)Btk轉(zhuǎn)錄及表達(dá),。同時，該研究發(fā)現(xiàn)Btk蛋白可以發(fā)生乙?；揎?，Btk蛋白的乙酰化可通過蛋白激酶Lyn影響B(tài)tk蛋白磷酸化,。這些結(jié)果拓展了對Btk調(diào)節(jié)及其功能的認(rèn)識,，并有益于對相關(guān)疾病的研究。
蛋白乙?；梢阴＾D(zhuǎn)移酶和去乙?；竸討B(tài)調(diào)節(jié)。進(jìn)一步的研究發(fā)現(xiàn)體內(nèi)與體外B細(xì)胞激活有意義的誘導(dǎo)細(xì)胞內(nèi)乙酰轉(zhuǎn)移酶活性增加,，但是去乙?；富钚圆⒉唤档停@一結(jié)果揭示了B細(xì)胞激活誘導(dǎo)的(組蛋白和非組蛋白)乙?；侨绾握{(diào)節(jié)的。這一結(jié)果亦有助于研究其他免疫細(xì)胞(如T細(xì)胞)激活的乙?；{(diào)節(jié),。
此外，這項研究還報道了組蛋白去乙?；敢种苿㏕SA誘導(dǎo)Btk mRNA降解,。有趣的是,，TSA的這一作用并非通過抑制組蛋白去乙酰化酶活性,。TSA被廣泛地應(yīng)用于基礎(chǔ)及臨床研究,。已知TSA可導(dǎo)致許多(2-10%)基因的mRNA水平降低，但通常認(rèn)為TSA是通過對組蛋白去乙?；富钚缘囊种破鹱饔玫?。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Immunology, 2009, doi:10.4049/jimmunol.0902324
Lysine Acetylation Regulates Bruton's Tyrosine Kinase in B Cell Activation
Zhijian Liu,* Antonello Mai, and Jian Sun*
*Laboratory of B-Cell and Autoantibody, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, and ?Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai JiaoTong University School of Medicine, Shanghai; Institute of Genetics and Developmental Biology, and Graduate School, Chinese Academy of Sciences, Beijing, China; and Dipartimento di Studi Farmaceutici, Universita degli Studi di Roma La Sapienza, Rome, Italy
Bruton's tyrosine kinase (Btk) is essential for BCR signal transduction and has diverse functions in B cells. Although Btk has been extensively studied, the role of lysine acetylation in Btk regulation has not been reported. In this study, we show that BCR cross-linking induces histone lysine acetylation at the Btk promoter, correlating with marked recruitment of histone acetyltransferase E1A-associated 300-kDa protein (p300) to the locus. These effects enhance Btk promoter activity and increase the expression of Btk mRNA and protein. Consistent with these results, activated B cells display increased p300 expression and total histone acetyltransferase activity in vitro and in vivo, resulting in global histone acetylation. Interestingly, we found that BCR signaling induces Btk lysine acetylation mediated by p300. Moreover, lysine acetylation of Btk promotes its phosphorylation. Together, our results indicate a novel regulatory mechanism for Btk transcription and reveal a previously unrecognized posttranslational modification of the Btk protein and its association with phosphorylation in B cell activation.
