Regulation of human β2-microglobulin transactivation in hematopoietic cells
Regulation of human β2-microglobulin transactivation in hematopoietic cells
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DOI：
10.1182/blood-2002-09-2924
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发表时间：
2003-04-15
期刊：
影响因子：
20.3
通讯作者：
Van den Elsen, PJ
中科院分区：
文献类型：
--
作者：
Gobin, SJP;Biesta, P;Van den Elsen, PJ
β（2）-微球蛋白（β（2）m）是主要组织相容性复合体（MHC）I类分子的伴侣，其在抗原呈递、免疫球蛋白转运和铁代谢中起中心作用。因此，重要的是β（2）m在执行这些功能的细胞（如造血细胞）中充分表达。在这项研究中，我们研究了β（2）m在淋巴细胞和骨髓细胞系中通过一个含有推定的E盒，Ets/干扰素刺激反应元件（ISRE）和kappaB位点的启动子的转录调控。在这里，我们表明，上游刺激因子1（USF 1）和USF 2结合到E盒和调节β（2）m的反式激活。核因子kappaB（NF-kappaB）亚单位p50和p65与kappaB盒结合，p65反式激活β（2）m。干扰素调节因子1（IRF 1）、IRF 2、IRF 4和IRF 8，但不包括PU.1，与Ets/ISRE结合，IRF 1和IRF 3是β（2）m的强反式激活剂。总而言之，所有3个框对于淋巴和骨髓细胞类型中β（2）m表达的组成性和细胞因子诱导水平都很重要。因此，β（2）m反式激活受重要转录途径的控制，这些转录途径在损伤、感染和炎症期间被激活。(C)2003年，美国血液学会。
beta(2)-Microglobulin (beta(2)m) is a chaperone of major histocompatibility complex (MHC) class I (-like) molecules that play a central role in antigen presentation, immunoglobulin transport, and iron metabolism. It is therefore of importance that beta(2)m is adequately expressed in cells that perform these functions, such as hematopoietic cells. In this study, we investigated the transcriptional regulation Of beta(2)m in lymphoid and myeloid cell lines through a promoter containing a putative E box, Ets/interferon-stimulated response element (ISRE), and kappaB site. Here we show that upstream stimulatory factor 1 (USF1) and USF2 bind to the E box and regulate beta(2)m transactivation. The nuclear factor kappaB (NF-kappaB) sub-units p50 and p65 bind to the kappaB box and p65 transactivates beta(2)m. Interferon regulatory factor 1 (IRFI), IRF2, IRF4, and IRF8, but not PU.1, bind to the Ets/ISRE, and IRF1 and IRF3 are strong transactivators Of beta(2)m. Together, all 3 boxes are important for the constitutive and cytokine-induced levels Of beta(2)m expression in lymphoid and myeloid cell types. As such, beta(2)m transactivation is under the control of important transcriptional pathways, which are activated during injury, infection, and inflammation. (C) 2003 by The American Society of Hematology.