IPO13

更新于：2025-05-07

基本信息

别名

IMP13、importin 13、Importin-13

+ [6]

简介

Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6 and probably other members of the paired homeobox family. Also mediates nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13.

关联

100 项与 IPO13 相关的临床结果

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100 项与 IPO13 相关的转化医学

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0 项与 IPO13 相关的专利（医药）

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项与 IPO13 相关的文献（医药）

2025-03-01·Journal of Global Antimicrobial Resistance

Mobilization of an ICEclc-Like Element as a Potential Mechanism for the Spread of IMP-13 Carbapenemase in Pseudomonas aeruginosa

Article

作者: Aillerie, Sabine ; Nikolski, Macha ; Metifiot, Mathieu ; Moulieras, Mikeldi ; Pereyre, Sabine ; Boureima-Abdou, Bachir ; Bientz, Léa ; Dubois, Véronique ; Guiraud, Jennifer ; Coulange-Mayonnove, Laure ; Guyet, Ulysse ; Groppi, Alexis ; Bébéar, Cécile

Carbapenem-resistant Pseudomonas aeruginosa is a global public health concern. IMP-13 is a carbapenemase that was described for the first time in 2001 but is often underestimated due to poor hydrolysis of carbapenems and a lack of molecular detection. The aim of this study was to characterize the genetic support of bla_IMP-13 in P. aeruginosa and to assess the ability of mobile genetic elements to disseminate this resistance. A retrospective analysis conducted between 2010 and 2020 revealed eight multiresistant P. aeruginosa isolates by their production of the carbapenemase IMP-13 in Bordeaux. Additionally, three of the studied isolates exhibited high-level resistance to imipenem and imipenem-relebactam that was linked to an insertion sequence in the oprD gene. Successful mating was achieved, and transconjugants and parental clinical isolate genomes were sequenced. All clinical isolates were found to be ST621 strains. The data revealed that bla_IMP-13 was carried on an Integrative and Conjugative Element (ICEclc-like) of 88,589 bp with a 62% GC content harboring 85 CDSs, and was inserted at the tRNA^Gly locus PA0729.1. The ICE was identical in the eight studied clinical isolates and in all the ST621 strains found in the databases. The conjugation rate was low, at approximately 10^-8 transconjugants per donor and ICE transfer appeared to mobilize some adjacent parental genes located immediately downstream of the ICE. In conclusion, these results suggest that even if the spread of bla_IMP-13 is mainly due to an epidemic ST621 clone, the mobilization of a bla_IMP-13-carrying ICEclc-like element is possible and should not be underestimated.

2025-02-01·Clinical and Translational Medicine

RNF31 induces paclitaxel resistance by sustaining ALYREF cytoplasmic–nuclear shuttling in human triple‐negative breast cancer

Article

作者: Chen, Xiangfu ; Huang, Shumei ; Wang, Rui ; Shi, Dongni ; Lin, Chuyong ; Chen, Boyu ; He, Lixin ; Deng, Pinwei ; Kong, Lingzhi ; Yang, Muwen ; Chen, Xuwei ; Li, Yue ; Wei, Weidong ; Shi, Yawei ; Li, Jun ; Song, Libing ; Jiang, Xingyu ; Dai, Shuqin

AbstractBackgroundResistance to paclitaxel‐based chemotherapy is the major obstacle in triple‐negative breast cancer (TNBC) treatment. However, overcoming paclitaxel resistance remains an unsolved problem. The present study aimed to determine whether paclitaxel treatment impairs Aly/REF export factor (ALYREF) cytoplasmic–nuclear shuttling, its mechanism, and the role of ubiquitinated ALYREF in paclitaxel resistance.MethodsThe subcellular proportion of ALYREF was detected in samples from patients with TNBC using immunohistochemistry to analyze the relationship between ALYREF distribution and paclitaxel response. Cell viability assays, immunofluorescence assays, quantitative real‐time reverse transcription PCR assays, western blotting, and terminal deoxynucleotidyl transferase nick‐end‐labelling assays were conducted to measure the biological function of the subcellular proportion of ALYREF and E3 ligase ring finger protein 31 (RNF31) on paclitaxel sensitivity in TNBC. The synergistic effects of an RNF31 inhibitor plus paclitaxel on TNBC were evaluated. Cox regression models were adopted to assess the prognostic role of RNF31 in TNBC.ResultsHerein, we showed that regulation of ALYREF cytoplasmic–nuclear shuttling is associated with the paclitaxel response in TNBC. In paclitaxel‐sensitive TNBC, ALYREF was trapped in the cytoplasm by paclitaxel, while in paclitaxel‐resistant TNBC, ALYREF was efficiently transported into the nucleus to exert its function, allowing the export of the mRNAs encoding paclitaxel‐resistance‐related factors, including tubulin beta 3 class III (TUBB3), stathmin 1 (STMN1), and microtubule‐associated protein Tau (TAU), ultimately inducing paclitaxel resistance in TNBC. Mechanistically, we found that RNF31 interacts with and ubiquitinates ALYREF, which facilitates ALYREF nuclear transportation via importin 13 (IPO13) under paclitaxel treatment. Notably, the RNF31 inhibitor and paclitaxel synergistically repressed tumour growth in vivo and in TNBC patient‐derived organoids. In addition, analysis of patients with TNBC showed that elevated RNF31 levels correlated with poor prognosis.ConclusionThese data indicated that RNF31‐mediated ALYREF ubiquitylation could represent a potent target to reverse paclitaxel resistance in TNBC.Key points

RNF31 facilitated ALYREF‐mediated PTX resistance in TNBC.

RNF31 promoted ALYREF nuclear transport via IPO13 in response to PTX treatment, subsequently enhancing the export of mRNAs encoding PTX resistance‐related factors, including TUBB3, STMN1, and TAU.

Blocking RNF31 trapped ALYREF in the cytoplasm and induced TNBC cell death upon PTX treatment.

Inhibiting RNF31 activity re‐sensitized PTX‐resistant TNBC to PTX treatment.

2024-12-01·Placenta

Circular RNA hsa_circ_0081343 modulates trophoblast autophagy through Rbm8a nuclear translocation

Article

作者: Li, Jing ; Hu, Haoyue ; Tang, Qiong ; Zheng, Linmei ; Zhong, Mei ; Fang, Junbo ; Liu, Jinfu ; Tang, Rong ; Ahmad, Fiaz

INTRODUCTIONFetal growth restriction (FGR) is a kind of obstetric complication that seriously endangers fetal life. Recent studies reported significant reduction of hsa_circ_0081343 in human placenta developed in FGR and is involved in cell migration, invasion, and apoptosis of trophoblast by acting as microRNA sponges. Autophagy is required for invasion of trophoblast cells and for vascular remodeling during placentation. In this study, we aimed to explore the mechanistic link between hsa_circ_0081343 and autophagy.METHODSWe investigated the interactions between hsa_circ_0081343 and RNA-binding proteins were studied by RNA pull-down assay, mass spectrometry and RNA immunoprecipitation assay. The mechanism of nuclear translocation of Rbm8a were assessed by reverse transcription-quantitative PCR, Western blot, immunofluorescence and Co-Immunoprecipitation. Western blot, immunofluorescence and transmission electron microscopy were performed to elucidate the mechanism underlying hsa_circ_0081343 and/or Rbm8a mediated regulation of autophagy.RESULTShsa_circ_0081343 served as an RNA-binding protein (RBP) sponge. RNA binding motif protein 8A (Rbm8a) was directly bound to hsa_circ_0081343 in the cytoplasm, while knockdown of hsa_circ_0081343 facilitated Rbm8a localization in the nucleus. We also identified Rbm8a as a potential import cargo for Importin13 (Ipo13), which transported Rbm8a across the nuclear membrane into the nucleus. Ipo13 recognized Rbm8a via a functional nuclear localization signal (NLS). Furthermore, the mechanistic study revealed that hsa_circ_0081343-mediated nuclear translocation of Rbm8a activated trophoblast autophagy.DISCUSSIONOur results suggest that hsa_circ_0081343 could bind to RBP and the interaction between hsa_circ_0081343 and Rbm8a participate in regulating autophagy. These findings offer novel molecular targets and insights for a potential therapeutic strategy against FGR.

项与 IPO13 相关的新闻（医药）

2025-04-15

·药物分子设计

张宏研究组揭示转录因子LIN-15B调控自噬活性及溶酶体功能

买科研服务（代计算、代测试、超算机时），送老李校长“科研理工男士情感课”第一性原理计算解决50年悬而未决难题：半导体中铜为何扩散更快？Ab initio及第一性原理入门参考书介绍《海贼王》告诉你，做科研为什么不能闭门造车……985博导亲测：用DeepSeek写国自然本子，3天完成30天工作量来自公众号：大屯路15号本文以传播知识为目的，如有侵权请后台联系我们，我们将在第一时间删除。责编 | 侯文茹自噬过程的关键步骤包括自噬体形成、自噬体与溶酶体融合以及溶酶体降解。自噬-溶酶体通路基因的转录调控是调节自噬活性的重要机制。已知哺乳动物中调控自噬-溶酶体通路基因转录的主要转录因子是TFEB，但线虫中TFEB同源物HLH-30主要参与衰老及应激条件下自噬的调控，而且hlh-30功能缺失的线虫并无明显自噬缺陷表型。因此，在线虫发育过程中是否存在其他转录调控因子来系统性调控自噬活性尚未可知。2025年4月2日，张宏研究团队在《Autophagy》杂志发表题为“T16G12.6/IMPORTIN 13-mediated cytoplasm-to-nucleus transport of the THAP transcription factor LIN-15B controls autophagy and lysosome function in C. elegans”论文揭示IMPORTIN-13（IPO-13）通过介导转录因子LIN-15B的核质转运调控线虫自噬活性与溶酶体功能。lin-15B属于SynMuv（synthetic multivulva）B基因，参与调节线虫外阴的正常发育、细胞周期进程、幼虫生长、生殖腺发生和咽部形态发生等过程。SynMuv B基因与SynMuv A或 SynMuv C基因同时丧失功能会导致多外阴缺陷表型。然而其他Synmuv基因功能缺失并不能抑制自噬突变体表型，提示SynMuv基因lin-15B在自噬调控方面具有特异性。lin-15B含有THAP结构域，在染色体分离、染色质修饰和转录调控中发挥作用。研究发现，IPO-13是LIN-15B的核输入蛋白，负责将LIN-15B从细胞质转运到细胞核中。在生理条件下，LIN-15B主要定位在细胞核中，抑制自噬溶酶体通路相关基因的表达，维持自噬基因的低转录水平，以确保自噬处于基础生理水平。在ipo-13突变体或饥饿线虫中，LIN-15B无法正常入核，在细胞核的表达水平降低，引起自噬基因的表达上调从而增加自噬通量。综上，该研究发现转录因子LIN-15B是调控线虫发育过程中自噬活性的关键因子，且LIN-15B的调控功能依赖于核转运蛋白IPO-13将其从细胞质运输到细胞核中，并且这一过程受营养状态调控。图. IPO-13通过介导LIN-15B的核质转运从而调控自噬活性的模型中国科学院生物物理研究所张宏研究员为该论文通讯作者，中国科学院生物物理研究所助理研究员马晓丽和博士研究生缑晓萌为论文的共同第一作者。本研究得到国家自然科学基金委、中国科学院重大科学基础设施基础研究项目和新基石科学基金会的资助。文章链接：https://www.tandfonline.com/doi/full/10.1080/15548627.2025.2482724

IPO专利侵权

2025-02-09

·今日头条

可克服紫杉醇耐药性！中山大学研究团队：揭示“最毒乳腺癌”潜在药物靶点

【导读】对紫杉醇为基础的化疗产生耐药性是三阴性乳腺癌（TNBC）治疗中的主要障碍。然而，克服紫杉醇耐药性仍是一个未解决的问题。 2月6日，中山大学研究团队在期刊《Clinical And Translational Medicine》上发表了研究论文，题为“RNF31 induces paclitaxel resistance by sustaining ALYREF cytoplasmic–nuclear shuttling in human triple-negative breast cancer”，本研究旨在确定紫杉醇治疗是否会影响 Aly/REF 出口因子（ALYREF）的细胞质 - 细胞核穿梭，其机制以及泛素化 ALYREF 在紫杉醇耐药性中的作用。数据表明，RNF31 介导的 ALYREF 泛素化可能是逆转三阴性乳腺癌对紫杉醇耐药性的有力靶点。 https://onlinelibrary.wiley.com/doi/full/10.1002/ctm2.70203 三阴性乳腺癌（TNBC）是乳腺癌亚型中最具侵袭性的，占所有乳腺癌病例的 15% 至 20%，也被称为“最毒乳腺癌”。鉴于雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体 2（HER2/ErbB2）均为阴性，以紫杉烷类药物（如紫杉醇和多西他赛）为基础的化疗仍是早期和转移性 TNBC 的主要治疗策略。不幸的是，尽管最初有反应，但肿瘤不可避免地会对紫杉烷治疗产生耐药性。在早期阶段，约 30% 的 TNBC 患者在五年内病情进展，五年无复发生存率约为 70%，总生存率约为 75%，这远低于 ERBB2+ 或 HR+ 乳腺癌。因此，在临床实践中确定对紫杉醇的耐药机制并尝试克服紫杉醇耐药性至关重要。紫杉醇通过多种复杂机制发挥抗肿瘤作用。面对紫杉醇施加的各种细胞压力，癌细胞会启动细胞凋亡或使细胞压力转向生存，从而获得紫杉醇耐药性。新出现的证据表明，乳腺癌细胞会发展出多种机制来对抗紫杉醇诱导的压力，例如增加微管动力学、适应氧化应激增加以及上调抗凋亡蛋白。可是，迄今为止，尚未出现逆转紫杉醇耐药性的策略。有证据表明，mRNA 加工和输出参与了对癌症治疗策略的耐药性诱导。然而，mRNA 输出复合物对微管抑制剂耐药性的影响却很少被研究。因此，确定在三阴性乳腺癌（TNBC）中是否存在以及是哪些 mRNA 输出亚基与紫杉醇耐药性相关，这一点非常重要。蛋白质翻译后修饰（PTM）是调节蛋白质亚细胞分布的关键机制之一，可能在调节应激诱导的运输中发挥作用。RNF31是线性泛素链组装复合物（LUBAC）的核心催化单元。先前的研究表明，RNF31 表达升高会加速肿瘤进展和治疗耐药。然而，RNF31 调节的细胞信号底物及其生物学功能尚不完全清楚。 RNF31 在体外促进了 ALYREF 介导的三阴性乳腺癌对紫杉醇的耐药性 01 为了探究 RNF31 是否参与 ALYREF 介导的三阴性乳腺癌（TNBC）对紫杉醇（PTX）的耐药性，研究人员首先通过qRT-PCR检测了紫杉醇处理后耐药细胞和亲代 MDA-MB-231 细胞中紫杉醇耐药相关因子的 mRNA 丰度。过表达 RNF31 可恢复亲代细胞中紫杉醇耐药相关因子的降低水平，特别是上调了微管蛋白 TUBB3、微管结合蛋白 STMN1 和 TAU 的表达水平。此外，在耐药细胞中，沉默 RNF31 降低了紫杉醇耐药相关因子的表达。由于 TUBB3、STMN1 和 TAU 这三种紫杉醇耐药相关因子在响应外源性 RNF31 表达时其表达变化最为显著，因此选择它们进行进一步研究。 RNF31 在体外促进了 ALYREF 介导的三阴性乳腺癌对紫杉醇的耐药性与亲代三阴性乳腺癌（TNBC）细胞相比，紫杉醇耐药的 TNBC 细胞中 TUBB3、STMN1 和 TAU 的水平显著升高。同样，在对基于紫杉醇的化疗耐药的 TNBC 患者中也观察到了 TUBB3、STMN1 和 TAU 水平的上调。TNBC 患者中 TUBB3、STMN1 和 TAU 的表达水平与核 ALYREF 水平显著相关。此外，通过核质分离和后续的 qRT-PCR 验证，用 siRNA 或噻唑菌素阻断 RNF31 或沉默 IPO13 均可降低 TUBB3、STMN1 和 TAU 的总 mRNA 水平和细胞质 mRNA 水平。研究人员接下来探究了 RNF31 和 IPO13 对 ALYREF 与 mRNA 结合的影响。抗 ALYREF 抗体介导的 RNA 免疫沉淀（RIP）-PCR 显示，在紫杉醇耐药的 MDA-MB-231 细胞中，阻断 RNF31 和沉默 IPO13 显著降低了 ALYREF 与 TUBB3、STMN1 和 TAU mRNA 的结合水平。相比之下，抑制 RNF31 和沉默 IPO13 促进了 Mtr4 外切体 RNA 解旋酶（MTREX，也称为 hMTR4）对 TUBB3、STMN1 和 TAU mRNA 的结合，MTREX 是细胞核内 mRNA 降解复合物的关键标志物。此外，在紫杉醇耐药的 MDA-MB-231 细胞中，抑制 RNF31 和沉默 IPO13 显著缩短了 TUBB3、STMN1 和 TAU mRNA 的半衰期。另外，在亲代细胞中，紫杉醇处理显著降低了 TUBB3、STMN1 和 TAU 的蛋白水平，而过表达 RNF31 恢复了亲代细胞中 TUBB3、STMN1 和 TAU 的降低水平。同时，抑制 ALYREF 表达消除了外源性 RNF31 表达对亲代细胞在紫杉醇处理时的影响。上述结果表明 RNF31 维持了 ALYREF 的 mRNA 结合和输出功能；因此，研究人员进一步研究了 ALYREF 是否影响亲代细胞在紫杉醇处理时 RNF31 的表达。研究显示，在紫杉醇耐药细胞中，沉默 ALYREF 和 IPO13 降低了 RNF31 mRNA 和蛋白水平，表明 RNF31 和 ALYREF 在紫杉醇耐药的三阴性乳腺癌细胞中形成正反馈环路。综上所述，上述结果表明 RNF31 通过上调与紫杉醇耐药相关的因子的表达，促进了 ALYREF 诱导的紫杉醇耐药性。【参考资料】 https://onlinelibrary.wiley.com/doi/full/10.1002/ctm2.70203 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。热门推荐活动点击免费报名 🕓 全国｜2024年12月-2025年03月 ▶ 中国转化医学产业大会 🕓 上海｜2025年02月28日-03月01日 ▶ 第四届长三角单细胞组学技术应用论坛暨空间组学前沿论坛点击对应文字查看详情

信使RNA免疫疗法