FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity
FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity
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DOI：
10.1007/s12026-008-8029-x
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发表时间：
2008-10-01
影响因子：
4.4
通讯作者：
Greene, Mark I.
中科院分区：
文献类型：
--
作者：
Zhou, Zhaocai;Song, Xiaomin;Greene, Mark I.
叉头盒蛋白P3（FOXP 3）有助于独特的转录特征，并作为CD 4（+）CD 25（+）天然调节性T细胞的功能标记。人类FOXP 3的功能障碍与称为免疫失调、多内分泌病、肠病、X连锁综合征（IPEX）或X连锁自身免疫-过敏失调综合征（XLAAD）的致命性自身免疫性疾病相关。FOXP 3还可以作为v-erb-b2成红细胞白血病病毒癌基因同源物2（神经/成胶质细胞瘤衍生的癌基因同源物（禽类））（Her 2/neu）基因的乳腺肿瘤抑制因子。虽然FOXP 3在维持耐受性和自身免疫之间的免疫平衡方面的抑制功能是明显的，但潜在的分子机制仍然几乎完全不确定。最近的研究表明FOXP 3可能与包括转录因子和酶蛋白在内的多种分子伴侣形成动态超分子复合物来调节转录。FOXP 3系综如何响应T细胞受体信号和/或促炎信号而变化仍不清楚，尽管该实验室的工作揭示了其复杂性。FOXP 3复合物的结构信息可能提供新的功能见解，以及促进发展合理的手段来调节各种人类疾病中的调节性T细胞功能。
Forkhead box protein P3 (FOXP3) contributes to a unique transcriptional signature and serves as a functional marker of CD4(+)CD25(+) natural regulatory T cells. Dysfunction of FOXP3 in human is associated with fatal autoimmune disease known as immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) or X-linked autoimmunity-allergic disregulation syndrome (XLAAD). FOXP3 also can act as a breast tumor suppressor of the v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog (avian)) (Her2/neu) gene. While the suppressive functions of FOXP3 in maintaining the immune balance between tolerance and autoimmunity are obvious, the underlying molecular mechanism remains almost entirely undefined. Recent studies indicate that FOXP3 may form a dynamic superamolecular complex with a variety of molecular partners including transcription factors and enzymatic proteins to regulate transcription. How the FOXP3 ensemble changes in response to T-cell receptor signals and/or proinflammatory signal remains unclear although work from this laboratory has revealed its complexity. Structural information on FOXP3 complex may offer novel functional insights, as well as facilitate the development of rational means to modulate regulatory T-cell function in various human diseases.