Th-Inducing POK Factor (ThPOK)是決定胸腺細(xì)胞向CD4 T細(xì)胞分化的重要轉(zhuǎn)錄因子,。其在分化過渡態(tài)細(xì)胞中開始表達(dá)，通過開啟CD4分化定向的基因同時關(guān)閉CD8分化定向的基因,，調(diào)控DP胸腺細(xì)胞的CD4/CD8定向分化,。ThPOK可以正調(diào)控自身的表達(dá)，但最后特異表達(dá)于CD4細(xì)胞,，而在CD8細(xì)胞中完全不表達(dá),。這種差異表達(dá)是如何在分化過程中建立的仍然不清楚。
該項研究揭示在DP胸腺細(xì)胞向CD4或CD8分化定向過程中,，ThPOK蛋白的穩(wěn)定性及乙?；揎椝降牟煌菍?dǎo)致其最終在CD4和CD8細(xì)胞中差異表達(dá)的可能原因。在CD4細(xì)胞中,，ThPOK高乙?；３址€(wěn)定,；相反,，在CD8細(xì)胞中，ThPOK低乙?；杆俳到?。因此，ThPOK表達(dá)的正反饋可以在CD4細(xì)胞中維持,，而在CD8細(xì)胞中被阻斷,。此外，該工作還揭示組蛋白乙?；竝300特異性地催化ThPOK的乙?；揎棧⑶彝ㄟ^競爭同一位點的泛素化修飾而增強ThPOK的穩(wěn)定性,。這項工作從蛋白的轉(zhuǎn)錄后修飾水平闡明了調(diào)控ThPOK穩(wěn)定性的一種新機制,，豐富了對胸腺細(xì)胞分化信號調(diào)控網(wǎng)絡(luò)的認(rèn)識。
該研究得到來自中國科學(xué)院,、科技部重大科學(xué)研究計劃,、國家自然科學(xué)基金委、上海市科委的經(jīng)費資助,。（生物谷Bioon.com）
生物谷推薦英文摘要：
The Journal of Immunology, 2010, doi:10.4049/jimmunol.1001462
p300-Mediated Acetylation Stabilizes the Th-Inducing POK Factor
Min Zhang, Jiali Zhang, Jinxiu Rui, and Xiaolong Liu
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
The lineage-specifying factor Th-inducing POK (ThPOK) directs the intrathymic differentiation of CD4 T cells. Although the regulation of ThPOK at the transcription level has been extensively studied, specific posttranslational modifications regulating the activity of ThPOK have not been addressed. In this paper, we show that ThPOK is an unstable protein that is more readily degraded in CD8 T cells compared with CD4 T cells. Among the various proteins that bind ThPOK, acetyltransferase p300 specifically promotes the acetylation of ThPOK at K210, K216, and K339, outcompeting ubiquitination, thereby stabilizing the protein. In CD4 T cells, attenuation of p300-mediated acetylation promotes the degradation of ThPOK. In contrast, mutation of lysines 210, 216, and 339 to arginines stabilizes ThPOK and enhances its ability to suppress the expression of CD8 molecule and cytotoxic effectors in CD8 T cells. Our results reveal an essential role of p300-mediated acetylation in regulating the stability of ThPOK and suggest that such regulation may play a part in CD4/CD8 lineage differentiation.
