美国纽约大学医学院Iannis Aifantis、Maria Guillamot以及宾夕法尼亚大学Luca Busino等研究人员，合作鉴定到E3泛素链接酶SPOP通过促进MYD88降解调控全身性炎症反应的消退。该项研究成果发表在2019年9月出版的《自然—免疫学》上。

研究人员揭示了E3泛素连接酶SPOP（Speckle-type BTB–POZ protein）抑制造血干细胞（HSC）的炎症活化。在没有SPOP的情况下，全身性炎症将无法缓解，并且HSC中的持续反应产生致死表型，这使人联想到过度炎症综合征或败血症。蛋白质组学研究揭示了SPOP通过泛素化先天信号转导蛋白MYD88（myeloid differentiation primary response protein 88）来限制炎症。这些发现揭示了HSC内在的翻译后机制，其对在紧急造血后重建体内平衡至关重要。

研究人员表示，对全身性感染和损伤的应答需要造血干细胞（HSC）的快速适应，这些HSC会增殖并将转向骨髓谱系分化。研究人员对了解触发紧急造血程序的信号具有浓厚的兴趣，因为这对于恢复体内平衡至关重要，然而，阻止HSC这种反应的机制仍然是未知的。

附：英文原文

Title: The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MYD88 degradation

Author: Maria Guillamot, Dahmane Ouazia, Igor Dolgalev, Stephen T. Yeung, Nikos Kourtis, Yuling Dai, Kate Corrigan, Luna Zea-Redondo, Anita Saraf, Laurence Florens, Michael P. Washburn, Anastasia N. Tikhonova, Marina Malumbres, Yixiao Gong, Aristotelis Tsirigos, Christopher Park, Christopher Barbieri, Kamal M. Khanna, Luca Busino, Iannis Aifantis

Issue&Volume: Volume 20 Issue 9

Abstract: The response to systemic infection and injury requires the rapid adaptation of hematopoietic stem cells (HSCs), which proliferate and divert their differentiation toward the myeloid lineage. Significant interest has emerged in understanding the signals that trigger the emergency hematopoietic program. However, the mechanisms that halt this response of HSCs, which is critical to restore homeostasis, remain unknown. Here we reveal that the E3 ubiquitin ligase Speckle-type BTB–POZ protein (SPOP) restrains the inflammatory activation of HSCs. In the absence of Spop, systemic inflammation proceeded in an unresolved manner, and the sustained response in the HSCs resulted in a lethal phenotype reminiscent of hyper-inflammatory syndrome or sepsis. Our proteomic studies decipher that SPOP restricted inflammation by ubiquitinating the innate signal transducer myeloid differentiation primary response protein 88 (MYD88). These findings unearth an HSC-intrinsic post-translational mechanism that is essential for reestablishing homeostasis after emergency hematopoiesis.

DOI: 10.1038/s41590-019-0454-6

Source:https://www.nature.com/articles/s41590-019-0454-6