E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses.
E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses.
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DOI：
10.1111/imr.12298
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发表时间：
2015-07
影响因子：
8.7
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Medvedev AE;Murphy M;Zhou H;Li X
Pellinos是E3泛素连接酶的一个家族，发现它们在催化Pelle的K63连接的多泛素化中起作用，Pelle是果蝇Toll途径中的IL-1受体相关激酶同源物。随后的研究揭示了哺乳动物Pellino-1、Pellino-2和Pellino-3在源自IL-1受体、Toll样受体、NOD样受体、T细胞和B细胞受体的信号传导途径中的中心和非冗余作用。虽然Pellinos与许多信号中间体相互作用的能力表明了它们的支架作用，但最近在表达连接酶失活的Pellinos的小鼠中的发现证明了Pellino泛素连接酶活性的重要性。Pellinos的细胞特异性功能已经出现，例如，Pellino-1是T淋巴细胞中的负调节剂和骨髓细胞中的正调节剂，并且已经揭示了Pellino家族的各种成员对受体信号传导的分子调节的细节。本文综述了Pellino通过模式识别受体、T细胞和B细胞受体以及TNF受体介导的信号调节作用，并讨论了Pellino在脓毒症和感染性疾病以及自身免疫性、炎症性和过敏性疾病中的作用。我们还提供了我们的观点与肽或小分子为基础的药物化合物靶向Pellinos作为一种新的治疗方法，脓毒性休克和自身免疫性病理学的潜力。
Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63-linked polyubiquitination of Pelle, an IL-1 receptor-associated kinase homologue in the Drosophila Toll pathway. Subsequent studies have revealed the central and non-redundant roles of mammalian Pellino-1, Pellino-2 and Pelino-3 in signaling pathways emanating from IL-1 receptors, Toll-like receptors, NOD-like receptors, T- and B-cell receptors. While Pellinos ability to interact with many signaling intermediates suggested their scaffolding roles, recent findings in mice expressing ligase-inactive Pellinos demonstrated the importance of Pellino ubiquitin ligase activity. Cell-specific functions of Pellinos have emerged, e.g., Pellino-1 being a negative regulator in T-lymphocytes and a positive regulator in myeloid cells, and details of molecular regulation of receptor signaling by various members of the Pellino family have been revealed. In this review, we have summarized current information about Pellino-mediated regulation of signaling by pattern recognition receptors, T-cell and B-cell receptors and TNF receptors, and discuss Pellino’s role in sepsis and infectious diseases, as well as in autoimmune, inflammatory and allergic disorders. We also provide our perspective on the potential of targeting Pellinos with peptide- or small molecule-based drug compounds as a new therapeutic approach for septic shock and autoimmune pathologies.
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影响因子：
8.7
作者：
Beutler B
通讯作者：
Beutler B
PELI1促进了TRIF依赖性Toll样受体信号传导和促炎性细胞因子的产生。
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
16
作者：
Damgaard, Rune Busk;Nachbur, Ueli;Gyrd-Hansen, Mads
通讯作者：
Gyrd-Hansen, Mads
影响因子：
30.5
作者：
Choi, Kyung-Chul;Lee, Youn Sook;Park, Seok Hee
通讯作者：
Park, Seok Hee