Center of Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Cell Rep. 2019 Apr 30;27(5):1461-1471.e4. doi: 10.1016/j.celrep.2019.04.014.
B cell lymphoma-6 (BCL6) is highly expressed in germinal center B cells, but how its expression is maintained is still not completely clear. Aryl hydrocarbon receptor interacting protein (AIP) is a co-chaperone of heat shock protein 90. Deletion of Aip in B cells decreased BCL6 expression, reducing germinal center B cells and diminishing adaptive immune responses. AIP was required for optimal AKT signaling in response to B cell receptor stimulation, and AIP protected BCL6 from ubiquitin-mediated proteasomal degradation by the E3-ubiquitin ligase FBXO11 by binding to the deubiquitinase UCHL1, thus helping to maintain the expression of BCL6. AIP was highly expressed in primary diffuse large B cell lymphomas compared to healthy tissue and other tumors. Our findings describe AIP as a positive regulator of BCL6 expression with implications for the pathobiology of diffuse large B cell lymphoma.
B 细胞淋巴瘤-6（BCL6）在生发中心 B 细胞中高度表达，但表达如何维持尚不完全清楚。芳香烃受体相互作用蛋白（AIP）是热休克蛋白 90 的共伴侣。在 B 细胞中删除 Aip 会降低 BCL6 的表达，减少生发中心 B 细胞并减弱适应性免疫反应。AIP 是 B 细胞受体刺激后 AKT 信号传导的最佳条件所必需的，并且 AIP 通过与去泛素酶 UCHL1 结合来保护 BCL6 免受 E3 泛素连接酶 FBXO11 介导的泛素蛋白酶体降解，从而有助于维持 BCL6 的表达。与健康组织和其他肿瘤相比，AIP 在原发性弥漫性大 B 细胞淋巴瘤中高度表达。我们的研究结果将 AIP 描述为 BCL6 表达的正调节剂，对弥漫性大 B 细胞淋巴瘤的病理生物学具有重要意义。
