更新于：2024-09-19

TRAF7

更新于：2024-09-19

基本信息

别名

DKFZp586I021、E3 ubiquitin-protein ligase TRAF7、MGC7807

+ [8]

简介

E3 ubiquitin ligase capable of auto-ubiquitination, following phosphorylation by MAP3K3. Potentiates MAP3K3-mediated activation of the NF-kappa-B, JUN/AP1 and DDIT3 transcriptional regulators (PubMed:14743216). Induces apoptosis when overexpressed (PubMed:15001576). Plays a role in the phosphorylation of MAPK1 and/or MAPK3, probably via its interaction with MAP3K3.

关联

100 项与 TRAF7 相关的临床结果

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100 项与 TRAF7 相关的转化医学

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0 项与 TRAF7 相关的专利（医药）

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143

项与 TRAF7 相关的文献（医药）

2024-07-02·Microbiology Spectrum

The Chlamydia trachomatis Inc Tri1 interacts with TRAF7 to displace native TRAF7 interacting partners

Article

作者: Sherry, Jessica ; Engel, Joanne ; Pha, Khavong ; Solomon, David ; Herrera, Clara M ; Stevers, Meredith ; Krogan, Nevan J ; McMahon, Eleanor ; Adams-Boone, Kathleen ; Elwell, Cherilyn ; Swaney, Danielle L ; Johnson, Jeffrey R

ABSTRACTChlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood. C. trachomatis accomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, the inc lusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor-associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated with C. trachomatis infection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen-activated protein kinase kinase kinase 2 (MEKK2), and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling during C. trachomatis infection. IMPORTANCEChlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between a C. trachomatis -secreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrated that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis of C. trachomatis infections but also in understanding the role of TRAF7 in cancer.

2024-07-01·No shinkei geka. Neurological surgery

[Current Status of Genetic/Molecular Abnormality Analysis and Prognosis Prediction of Meningioma].

Review

作者: Okano, Atsushi

Biological molecular studies of meningiomas have also developed with the development of molecular biological methods. In 2013, Clark et al. reported that driver genetic mutations other than NF2, including TRAF7, KLF4, AKT1, and SMO, were associated with meningioma development. In 2017, Sahm et al. proposed a classification of meningiomas based on global methylation status, which was more accurate in predicting prognosis than conventional WHO grading. In 2022, based on this classification, various groups reported an integrated classification that comprehensively included some biological molecular abnormalities, such as DNA mutations, copy number alterations, and RNA sequences. This field is expected to elucidate the mechanism of meningioma development and further research is expected to lead to the development of effective molecularly targeted therapeutics and biomarkers of radiosensitivity in the future. In this article, we summarize the current status and prospects of these biological molecular studies.

2024-07-01·Journal of Molecular Cell Biology

The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development

Article

作者: Lu, Qing ; Wu, Shengnan ; Hu, Ruixing ; Song, Xiaozhen ; Xiao, Man ; Zhang, Hong ; Chen, Yi

AbstractTRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways, contributing to immune responses, tumor progression, and embryonic development. Somatic mutations within the coiled-coil (CC) domain and WD40 repeat domain of TRAF7 could cause brain tumors, while germline pathogenic mutations contribute to severe developmental abnormalities. However, the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains unclear. In this study, we employed zebrafish as an in vivo model system. TRAF7 knock down caused defects in zebrafish embryonic development. We determined the crystal structure of TRAF7 CC domain at 3.3 Å resolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic development. Additionally, disease-causing mutations in TRAF7 CC region could impair the trimer formation, consequently impacting early embryonic development of zebrafish. Therefore, our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.

项与 TRAF7 相关的新闻（医药）

2022-07-19

·药时代

iPS干细胞治疗糖尿病，竟导致患者出现肿瘤？

2006年，日本京都大学山中伸弥教授在 Cell 期刊发表论文，发现将 Oct3/4、Sox2、Klf4、c-Myc 这四种转录因子通过病毒载体导入成熟体细胞后，可将体细胞转化为诱导多能干细胞（iPSC）。山中伸弥因此获得了2012年诺贝尔生理学或医学奖，也开启了 iPSC 治疗的新时代。近年来，基于 iPSC 的 CAR-T、CAR-NK 细胞疗法，以及再生医学和抗衰老研究如火如荼。然而，诱导的 iPSC 可能存在细胞过度生长和癌变风险，因此具有潜在致癌性。早在2009年，山中伸弥就曾在 Nature Biotechnology 期刊发表论文，显示胚胎成纤维细胞来源的 iPS 神经干细胞植入小鼠后，具有较高的成瘤风险。近日，Stem Cells and Development 期刊发表了一篇题为：Distinctive Clinical and Pathologic Features of Immature Teratomas Arising from Induced Pluripotent Stem Cell-Derived Beta Cell Injection in a Diabetes Patient 的论文。尽管目前有许多基于 iPSC 的细胞疗法的临床试验，但仍不清楚是否会在患者中发生真正的肿瘤。这篇论文报告了第一例 iPSC 来源细胞治疗2型糖尿病后形成未成熟畸胎瘤的临床病例。与成熟畸胎瘤不同，未成熟畸胎瘤具有复发和转移的潜力，论文作者强调，在使用 iPSC 细胞治疗时，应当更加关注畸胎瘤的形成，并进一步探索治疗的安全性和有效性。糖尿病是一种以高血糖、胰岛素抵抗和血糖调节缺陷为特征的代谢性疾病，可损害各种器官功能。据WHO预测，到2030年，全球糖尿病患者人数将翻一番，造成严重的社会经济负担。2型糖尿病（T2DM）占所有糖尿病病例的85%-95%，其特征是胰岛素抵抗和胰腺β细胞的胰岛素分泌受损，多数患者需要终生接受胰岛素注射来控制血糖，这常导致不可逆胰腺β细胞损伤并引起严重并发症。近年来，越来越多的研究开始聚焦于使用人诱导多能干细胞（hiPSC）来源的β细胞来治疗胰岛中不可逆的β细胞损伤，并被认为是治愈糖尿病的有潜力的方法。然而，iPSC 的致瘤性一定程度上阻碍了其临床应用，在体外和体内 iPSC 实验模型中，已检测到其存在广泛的基因组不稳定性，包括染色体畸变、拷贝数变异和单核苷酸变异等，小鼠模型实验也观察到了存在致瘤性，此外，还有少数临床试验病例报道了 iPSC 来源的细胞在移植后形成肿瘤或肿瘤样病变。但目前还没有 iPSC 治疗2型糖尿病后导致患者出现肿瘤的病例报道。这篇论文报道了一例2型糖尿病患者在接受 iPSC 来源细胞治疗后形成未成熟畸胎瘤的病例。该2型糖尿病患者接受移植的β细胞是由自体 iPSC 分化而来，2020年6月，该患者在北京的某家医院接受了自体 iPSC 来源的β细胞的注射，病历显示，该患者血液中分离的体细胞被重编程为 iPSC，然后再分化为胰岛β细胞，在扩增后通过左上臂的三角肌注射到患者体内。到治疗后2个月，患者的血糖调节和胰岛素水平并没有改善，反而在注射位置出现肿块以及腋窝淋巴结肿大。此后，这名患者来到了云南省肿瘤医院接受了治疗（该患者的iPSC治疗并非在云南省肿瘤医院进行）。磁共振成像（MRI）扫描提示，该肿瘤为良性或中间性肿瘤。2020年8月，患者接受了肿瘤切除手术，病理诊断显示是未成熟畸胎瘤。PET-CT 检查显示存在同侧腋窝和颈部淋巴结转移。经过两个周期的常规化疗后，患者的肿瘤出现进展。此后患者接受了颈部和腋窝手术区的辅助放疗，并结合化疗。到2021年10月，PET-CT 显示患者没有出现肿瘤复发或远端转移。为了确定畸胎瘤中是否存在胰岛β细胞，通过免疫荧光测定检测诱导的 iPSC 的关键标志物 OCT4 和 SOX2 基因表达，二者在细胞核或细胞质中均呈阳性。然而，对肿瘤细胞中胰岛素的免疫组织化学染色呈阴性。OCT4 和 SOX2 阳性，表明注射后的细胞并未完全分化。而胰岛素阴性表明这些细胞没有产生胰岛素分泌功能，这说明 iPSC 在体外诱导的状态不代表在体内植入后的状态。对患者的肿瘤组织进行的高通量测序显示，患者肿瘤细胞中存在 ABCB4、CDC73、CROT、DNMT3A、HCK、KMT2D、MSH2、MSH6、NCOR2、PRDM1、PREX2、RPS6KB2、TRAF7、ZFHX3、ZNF703 和 ZRSR2 这16个基因的错义或移码突变。iPSC 来源的细胞疗法已经在临床试验中显示了对癌症、神经图形学疾病以及糖尿病的疗效。与其他干细胞疗法相比，iPSC 细胞具有更易获取、扩增迅速、免疫原性低、无伦理问题等显著优势。然而，基于 iPSC 的细胞治疗具有致瘤性的潜在风险，这是其在推广到临床过程中面临的一大障碍。越来越多的证据表明，iPSC 的重编程会带来潜在致瘤性风险，例如病毒载体带来的基因插入、转录因子的长期过表达等等。2022年4月，Altos Labs 公司在 Nature Aging 发表的一项研究显示【2】，通过瞬时表达重编程因子（Oct4、Sox2、Klf4 和 c-Myc）对衰老小鼠进行体内重编程，恢复了衰老细胞的年轻表观遗传特征，并延长了早衰小鼠模型寿命。这提示了我们，瞬时诱导方案效果良好，且没有观察到致瘤性等潜在副作用。最后，论文作者总结道，在 iPSC 来源的β细胞治疗糖尿病后，应更加关注畸胎瘤的形成，因为形成的未成熟畸胎瘤比典型的成熟畸胎瘤更具侵袭性。应在标准临床试验中进一步探索 iPSC 来源细胞治疗糖尿病的安全性和有效性。论文链接：1.https://www.liebertpub.com/doi/10.1089/scd.2021.02552.https://www.nature.com/articles/s43587-022-00183-2版权声明/免责声明本文为授权转载文章，版权归拥有者。仅供感兴趣的个人谨慎参考，非商用，非医用、非投资用。欢迎朋友们批评指正！衷心感谢！文中图片、视频为授权正版作品，或来自微信公共图片库，或取自公司官网/网络根据CC0协议使用，版权归拥有者。任何问题，请与我们联系（电话：13651980212。微信：27674131。邮箱：contact@drugtimes.cn）。衷心感谢！推荐阅读首款国产新冠中和抗体，不仅是抗疫的新助力，更是新药研发成功的经典案例...重磅信号！四环医美+生物医药双轮驱动战略迈出坚实步伐热烈祝贺「中国肝病新药联盟」成立！新一届组委会诞生！智慧芽创始人、CEO张济徽：生物医药，智慧芽笃定的未来黎健博士 | 生子当如布鲁斯！——诺贝尔奖得主Bruce Beutler教授的故事热烈祝贺《中国药理学报》「NASH专刊」出版！十多位专家分享真知灼见，中国NASH新药联盟和药时代全力协助PD-1出海接力赛：FDA官网更新了「7月12日批准」的药物名单，没有百济神州...Moderna突破Moderna！变革从新品牌、新Logo开始。。。沙利文发布《眼科药物市场发展现状与未来趋势研究报告》（内附完整报告获取方式）如何解读反弹后稳住的恒瑞医药当出海已经关乎药企的「生与死」，我们还能如何寻求助力？| 药时代出海系列阿尔茨海默病：何以解忧，唯有新药集采第七轮来临，恒瑞业绩拐点究竟何在？2100万美元收购！Portage Biotech全力以赴地投身于腺苷通路点击这里，欢聚药时代！

细胞疗法抗体免疫疗法并购放射疗法