中科院上海生命科学院、上海交通大学医学院健康科学研究所的研究人员发现了酪氨酸蛋白激酶Btk转录调节的新机制：组蛋白乙酰转移酶p300介导的组蛋白乙酰化正调，而组蛋白去乙酰化酶1介导的组蛋白去乙酰化负调Btk转录及表达。这些结果拓展了对Btk调节及其功能的认识，并有益于对相关疾病的研究。
这一研究成果公布在美国免疫学会会刊《免疫学杂志》(Journal of Immunology)上，领导这一研究的是上海交通大学医学院上海市免疫研究所研究员孙健博士，其早年毕业于遵义医学院，曾发现并鉴定了一种新的系统性红斑狼疮单基因缺失小鼠模型---转录因子Aiolos基因敲除小鼠。
酪氨酸蛋白激酶Btk在B细胞受体信号传导中起重要作用。Btk基因突变导致人与小鼠发生免疫缺陷。该项研究揭示了Btk转录调节的新机制—组蛋白乙酰转移酶p300介导的组蛋白乙酰化正调，而组蛋白去乙酰化酶1介导的组蛋白去乙酰化负调Btk转录及表达。同时，该研究发现Btk蛋白可以发生乙酰化修饰，Btk蛋白的乙酰化可通过蛋白激酶Lyn影响Btk蛋白磷酸化。这些结果拓展了对Btk调节及其功能的认识，并有益于对相关疾病的研究。
蛋白乙酰化由乙酰转移酶和去乙酰化酶动态调节。进一步的研究发现体内与体外B细胞激活有意义的诱导细胞内乙酰转移酶活性增加，但是去乙酰化酶活性并不降低，这一结果揭示了B细胞激活诱导的(组蛋白和非组蛋白)乙酰化是如何调节的。这一结果亦有助于研究其他免疫细胞(如T细胞)激活的乙酰化调节。
此外，这项研究还报道了组蛋白去乙酰化酶抑制剂TSA诱导Btk mRNA降解。有趣的是，TSA的这一作用并非通过抑制组蛋白去乙酰化酶活性。TSA被广泛地应用于基础及临床研究。已知TSA可导致许多(2-10%)基因的mRNA水平降低，但通常认为TSA是通过对组蛋白去乙酰化酶活性的抑制起作用的。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
