RNF152

更新于：2025-05-07

基本信息

别名

E3 ubiquitin-protein ligase RNF152、FLJ39176、ring finger protein 152

+ [2]

简介

E3 ubiquitin-protein ligase that acts as a negative regulator of mTORC1 signaling by mediating ubiquitination of RagA/RRAGA and RHEB (PubMed:25936802, PubMed:30514904). Catalyzes 'Lys-63'-linked polyubiquitination of RagA/RRAGA in response to amino acid starvation, thereby regulating mTORC1 signaling (PubMed:25936802). Also mediates monoubiquitination of RHEB, promoting its association with the TSC-TBC complex and subsequent inhibition (PubMed:30514904). Also mediates 'Lys-48'-linked polyubiquitination of target proteins and their subsequent targeting to the proteasome for degradation (PubMed:21203937). Induces apoptosis when overexpressed (PubMed:21203937).

关联

项与 RNF152 相关的药物

KRAS G12D LYMTAC (Amgen)

KRAS G12D LYMTAC(安进制药)

靶点

KRAS G12D x RNF152

作用机制

KRAS G12D抑制剂 [+1]

在研机构

Amgen, Inc.

原研机构

Amgen, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 RNF152 相关的临床结果

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100 项与 RNF152 相关的转化医学

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0 项与 RNF152 相关的专利（医药）

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项与 RNF152 相关的文献（医药）

2024-09-02·British Poultry Science

Molecular and transcriptomic analysis of the ovary during laying and brooding stages in Zhedong white geese ( Anser cygnoides domesticus )

Article

作者: Zang, Z ; Liu, G ; Li, B ; Wang, S ; Wang, Y ; Huang, H ; Zhao, X

1. This study investigates the molecular mechanisms affecting brooding in Zhedong white geese by examining differences in reproductive endocrine levels, ovarian histology and transcriptomics.2. Twenty 18-month-old Zhedong white geese were selected to examine their ovaries using histological, biochemical, molecular biological, and high-throughput sequencing techniques during the laying and brooding periods.3. The results showed that the number of atretic follicles and apoptotic cells in the ovaries increased significantly (p < 0.05), the levels of follicle-stimulating hormone, luteinising hormone, gonadotropin-releasing hormone and oestradiol decreased significantly (p < 0.05), and the level of prolactin increased significantly (p < 0.01) during the brooding stage.4. In broody geese, the expression of CASP3, CASP9, P53, BAX, and Cyt-c were considerably higher (p < 0.05), but BCL2 expression was significantly lower (p < 0.05).5. In ovarian tissues, 260 differentially expressed lncRNAs, 13 differentially expressed miRNA and 60 differentially expressed mRNA were all discovered using transcriptome sequencing analysis. Functional enrichment analysis revealed that the differentially expressed mRNA and non-coding RNA target genes were primarily involved in ECM-receptor interaction, cell adhesion, cardiac muscle contraction, mTOR signalling, and the calcium signalling pathway.6. In conclusion, follicular atrophy and apoptosis occurred in the ovaries and serum reproductive hormone levels were significantly changed during the brooding period of Zhedong white geese. COL3A1, COL1A2, GRIA1, RNF152, miR-192, and miR-194 may be important candidates for the regulation of brooding behaviour, with the mTOR signalling pathway playing a key role.

2024-05-01·iScience

Fasting-induced RNF152 resensitizes gallbladder cancer cells to gemcitabine by inhibiting mTORC1-mediated glycolysis

Article

作者: Shen, Sheng ; Zan, Rui ; Sun, Wentao ; Lu, Xiao ; Liu, Han ; Shu, Mengxuan ; Ding, Yaqi ; Tao, Ying ; Gong, Zijun ; Liu, Houbao ; Zheng, Bohao ; Ma, Chaolin ; Ni, Xiaoling ; Suo, Tao

Abnormal mTORC1 activation by the lysosomal Ragulator complex has been implicated in cancer and glycolytic metabolism associated with drug resistance. Fasting upregulates RNF152 and mediates the metabolic status of cells. We report that RNF152 regulates mTORC1 signaling by targeting a Ragulator subunit, p18, and attenuates gemcitabine resistance in gallbladder cancer (GBC). We detected levels of RNF152 and p18 in tissues and undertook mechanistic studies using activators, inhibitors, and lentivirus transfections. RNF152 levels were significantly lower in GBC than in adjacent non-cancer tissues. Fasting impairs glycolysis, induces gemcitabine sensitivity, and upregulates RNF152 expression. RNF152 overexpression increases the sensitivity of GBC cells to gemcitabine, whereas silencing RNF152 has the opposite effect. Fasting-induced RNF152 ubiquitinates p18, resulting in proteasomal degradation. RNF152 deficiency increases the lysosomal localization of p18 and increases mTORC1 activity, to promote glycolysis and decrease gemcitabine sensitivity. RNF152 suppresses mTORC1 activity to inhibit glycolysis and enhance gemcitabine sensitivity in GBC.

2023-10-01·The American Journal of Pathology

RNF152 Suppresses Fatty Acid Oxidation and Metastasis of Lung Adenocarcinoma by Inhibiting IRAK1-Mediated AKR1B10 Expression

Article

作者: Zhao, Yang ; Yang, Zhichang ; Yang, Yang ; Zhu, Dengyan ; Nie, Yunfei ; Chen, Xiaoming

Lung adenocarcinoma (LUAD) is a common subtype of primary lung cancer. Fatty acid oxidation plays a key role in LUAD development by providing energy for tumor cells. This study aimed to identify the role of ring finger protein 152 (RNF152) in LUAD. RNF152 was down-regulated in LUAD, and low RNF152 expression correlated with a poor prognosis in LUAD patients. RNF152 overexpression inhibited the proliferation and malignant phenotype of LUAD cells, whereas RNF152 knockdown exerted an opposite effect. Tumor cells overexpressing RNF152 showed less fatty acid oxidation compared with control cells, whereas RNF152 knockdown induced fatty acid uptake and oxidation. Further analysis revealed the binding reaction between RNF152 and interleukin-1 receptor-associated kinase 1 (IRAK1). RNF152 reduced the stability of IRAK1 in LUAD cells by promoting its ubiquitination. RNF152-overexpressed tumor cells exhibited a significantly lower level of Aldo-Keto reductase family 1 member 10 (AKR1B10), whereas up-regulation of IRAK1 restored the expression of AKR1B10 in RNF152-overexpressed cells. Furthermore, up-regulation of IRAK1 eliminated the antitumor effect of RNF152 in LUAD cells. Mouse xenograft models confirmed the inhibitory effect of RNF152 on the tumorigenesis and metastasis of LUAD. Taken together, RNF152 played a tumor suppressive role in LUAD by promoting IRAK1 ubiquitination and IRAK1-mediated down-regulation of AKR1B10, thereby reversing the malignant phenotype of LUAD.

项与 RNF152 相关的新闻（医药）

2024-07-09

·药精通Bio

赞！曹雪涛团队一天2篇高水平文章

TIS2024第四届免疫细胞疗法与干细胞疗法论坛重磅来袭，详询：王晨 180 1628 8769 文章来源： iNature iNature 作为一个高度组织化的系统，内溶酶体在维持免疫稳态中起着至关重要的作用。然而，调节内溶酶体进展和随后的炎症反应的机制尚不完全清楚。 2024年6月21日，中国医学科学院/北京协和医学院曹雪涛及姜明红共同通讯在Advanced Science 在线发表题为“E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP-1 Proteasomal Degradation”的研究论文，该研究通过筛选调节内溶酶体酸化的103个E3泛素连接酶，发现溶酶体RNF13抑制溶酶体成熟，促进巨噬细胞内体Toll样受体(TLRs)介导的炎症反应。在机制上，RNF13介导K48连接的LAMP-1在K128残基上的多泛素化，用于蛋白酶体降解。TLR激活后，LAMP-1促进溶酶体成熟，从而加速了TLR的溶酶体降解，减少了巨噬细胞中TLR的信号传导。此外，类风湿关节炎(RA)患者外周血单个核细胞(PBMCs)显示RNF13水平升高，LAMP-1表达降低。因此，免疫抑制剂羟氯喹(HCQ)可增加RNF13的多泛素化。综上所述，该研究建立了蛋白酶体和溶酶体降解机制之间的联系，以诱导适当的先天免疫反应，并为靶向细胞内TLRs治疗炎症性疾病提供了一种有希望的方法。另外，2024年6月21日，中国医学科学院/北京协和医学院/南开大学/海军军医大学曹雪涛团队（徐贺楠和张晓为论文共同第一作者）在Immunity 在线发表题为“Cellular spermine targets JAK signaling to restrain cytokine-mediated autoimmunity”的研究论文，该研究通过对IFN-β激活的巨噬细胞的代谢组学分析和IFN刺激的反应因子报告因子筛选，发现精胺是Janus激酶(JAK)信号传导的代谢产物。精胺直接结合JAK1的FERM和SH2结构域，破坏JAK1-细胞因子受体的相互作用，从而广泛抑制细胞因子IFN-I、IFN-II、白细胞介素(IL)-2和IL-6引发的JAK1磷酸化。精胺浓度降低的SLE患者外周血单个核细胞(PBMCs)表现出IFN-I和狼疮基因特征的增强。精胺治疗减轻SLE和牛皮癣小鼠的自身免疫发病机制，降低SLE患者单核细胞中的IFN-I信号。研究人员合成了一种精胺衍生物(精胺衍生物1 [SD1])，并证明其具有有效的免疫抑制功能。总之，该研究结果表明精胺是细胞稳态的代谢检查点和控制自身免疫性疾病的潜在免疫抑制分子（点击阅读）。 Toll样受体(TLRs)是一个保守的模式识别受体(PRRs)家族，通过识别病原体相关的分子模式(PAMPs)，是宿主抵御外部病原体损伤的第一道防线。TLRs还可以识别内部损伤相关分子模式(DAMPs)，导致炎症反应的诱导。TLRs的完全激活是宿主消灭入侵病原体所必需的；然而，TLRs的不适当激活或过度刺激可导致慢性炎症性疾病、癌症和自身免疫性疾病的发生和发展。因此，严格和精确地调控TLR信号通路对于维持TLR信号的激活和抑制在免疫防御和疾病发病中的平衡至关重要。 TLRs是I型跨膜蛋白，由配体结合域和细胞内Toll/白细胞介素1 (IL-1)受体(TIR)同源域组成。大多数TLRs (TLR1, 2, 4, 5和6)在细胞表面表达，在那里它们被证明可以检测微生物的膜成分，如脂质，脂蛋白和蛋白质。在这些表面TLRs中，TLR4可以内化并易位到Rab5-和EEA1阳性的早期内体，在那里它与TRAM和TRIF相互作用，并在激活后启动TRIF依赖的信号传导。TLRs的其他亚群，包括TLR3、TLR7/8和TLR9，定位于细胞内室，如内质网(ER)、内体或溶酶体，主要负责微生物核酸检测，并启动下游信号传导，导致炎症细胞因子、I型干扰素(IFN-I)和趋化因子的分泌。文章模式图（图源自Advanced Science ）酸化是核内体成熟的关键过程。bafilomycin A1 (Baf-A1)等药物可以中和核内体和溶酶体的pH，阻断TLR信号传导。近年来，一些内溶酶体蛋白，如Lyst和Vps33B被报道在内溶酶体成熟动力学中起关键作用。此外，内核体/溶酶体晚期定位的Rab7b通过增强TLRs向内核体/溶酶体的运输并促进TLRs的降解，在巨噬细胞中作为TLR4或TLR9信号的负调节因子。然而，TLR活化对溶酶体酸化和生物发生的调节的详细机制仍未完全阐明。泛素化是一种广泛的翻译后修饰(PTM)，在调节功能蛋白的活性中起着关键作用，因此与多种细胞过程密切相关，包括蛋白质降解和运输。泛素(Ub)与底物的最终结合需要Ub激活酶(E1)、Ub偶联酶(E2)和Ub连接酶(E3)的连续作用。RNF家族包含一个N端RING结构域，是最大的E3泛素连接酶家族。一些定位于内体或溶酶体膜的RNF家族成员，如ZNRF1、ZNRF2、RNF152、RNF167和RNF13，以蛋白酶体依赖的方式进行广泛的蛋白质水解。溶酶体RNF13蛋白与肿瘤发生、内质网应激和肌生成有关。RNF13蛋白的C端含有一个RING结构域，该结构域可能使生物合成途径细胞器中的底物泛素化，但这种溶酶体泛素连接酶的底物尚未确定。该研究通过高含量筛选(HCS)研究了小鼠RING结构域E3家族在调节内溶酶体酸化中的功能，发现RNF13通过介导K48连接的多泛素化和LAMP-1的蛋白酶体降解来促进内体TLRs信号传导。LAMP-1促进溶酶体的酸化和成熟，缩短TLRs在早期内体中的保留时间，并增加转运到溶酶体室进行降解。总之，该研究揭示了一种新的TLR信号调节机制，该机制结合蛋白酶体和溶酶体诱导最佳免疫反应，为控制炎症性疾病提供了潜在的靶点。参考消息： https://onlinelibrary.wiley.com/doi/10.1002/advs.202309560 END 免责声明：来源干细胞之父平台往期发布内容，本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 TIS2024第四届免疫细胞疗法与干细胞疗法论坛重磅来袭，详询：王晨 180 1628 8769

细胞疗法免疫疗法