STK24

更新于：2025-05-07

基本信息

别名

Mammalian STE20-like protein kinase 3、Mammalian STE20-like protein kinase 3 C-terminal、Mammalian STE20-like protein kinase 3 N-terminal

+ [16]

简介

Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Regulates also cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753).

关联

项与 STK24 相关的药物

JA-310

靶点

STK24

作用机制

STK24调节剂

在研机构

Johann Wolfgang Goethe-Universität Frankfurt am Main

原研机构

Johann Wolfgang Goethe-Universität Frankfurt am Main

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 STK24 相关的临床结果

登录后查看更多信息

100 项与 STK24 相关的转化医学

登录后查看更多信息

0 项与 STK24 相关的专利（医药）

登录后查看更多信息

565

项与 STK24 相关的文献（医药）

2025-03-21·Environmental Technology

Controlling the amount of MoSe ₂ loaded SrTiO ₃ to activate peroxymonosulfate for efficient elimination of organic pollutants

Article

作者: Yang, Fei ; Zhu, Yueming ; Gao, Yuexiang

It is critical to effectively eliminate recalcitrant organic pollutants from wastewater. In this paper, the MoSe₂/SrTiO₃ (MST) catalysts were synthesized through simply controlling the amount of MoSe₂ in the hydrothermal method to activate peroxymonosulfate (PMS) for the degradation of pollutants. The results demonstrated that sulfamethoxazole and tetracycline were almost eliminated by PMS/MST-3 (MoSe₂/SrTiO₃ mass ratio 0.3: 1) activation system. The effect of inorganic anions (Cl ^-, H₂PO₄ ^-, HCO₃ ^-) and metal ions (Cu²⁺, Ni²⁺, Zn²⁺) commonly found in actual water bodies on catalytic reaction was explored. Moreover, SO₄^{• -}, ^•OH and ¹O₂ were identified by EPR tests and scavenger experiments, where the SO₄^{• -} and ^•OH were the dominant reactive species. The XPS analysis indicated that the oxygen vacancies and charge transfer on the catalyst surface were the keys of PMS activation. The effect of active sites in SMX and TC on the catalytic degradation activity was explored by density functional theory, and it was obtained that the central nitrogen site of SMX was more vulnerable in the catalytic system, while the edge oxygen site of TC was more susceptible to attack.

2025-02-01·Translational Oncology

Role of 3-mercaptopyruvate sulfurtransferase in cancer: Molecular mechanisms and therapeutic perspectives

Review

作者: Zhu, Yi-Wen ; Wang, Jun ; Li, Yan ; Feng, Zhi-Fen ; Liang, Xiao-Yi ; Liu, Zi-Hui ; Yang, Yi-Lun ; Jiang, Qi-Ying ; Jiang, Tong ; Tang, Ao-Qi ; Zhou, Ze-Tao ; Wu, Dong-Dong ; Zhang, Ka

The occurrence and development of tumor is mediated by a wide range of complex mechanisms. Subsequent to nitric oxide and carbon monoxide, hydrogen sulfide (H₂S) holds the distinction of being the third identified gasotransmitter. Alternation of H₂S level has been widely demonstrated to induce an array of disturbances in important cancer cell signaling pathways. As a result, the effects of H₂S-catalyzing enzymes in cancers also attract widspread attention. 3-mercaptopyruvate sulfurtransferase (3-MST) is privileged to be one of them. In fact, 3-MST is overexpressed in many tumors including human colon cancer, lung adenocarcinoma, and bladder urothelial carcinoma. But it is also lowly expressed in hepatocellular carcinoma. In this review, we focus on the generation of endogenous H₂S and polysulfides, facilitated by 3-MST. Additionally, we delve deeply into the potential role of 3-MST in tumorigenesis and development. The impact of 3-MST inhibition on the development of tumors and its potential for tumor therapy are also highlighted.

2025-02-01·Redox Biology

Polysulfide and persulfide-mediated activation of the PERK-eIF2α-ATF4 pathway increases Sestrin2 expression and reduces methylglyoxal toxicity

Article

作者: Ogasawara, Yuki ; Kimura, Hideo ; Koike, Shin

Unfolded protein response (UPR) is activated in cells under endoplasmic reticulum (ER) stress. One sensor protein involved in this response is PERK, which is activated through its redox-dependent oligomerization. Prolonged UPR activation is associated with the development and progression of various diseases, making it essential to understanding the redox regulation of PERK. Sulfane sulfur, such as polysulfides and persulfides, can modify the cysteine residues and regulate the function of various proteins. However, the regulatory mechanism and physiological effects of sulfane sulfur on the PERK-eIF2α-ATF4 pathway remain poorly understood. This study focuses on the persulfidation of PERK to elucidate the effects of polysulfides on the PERK-eIF2α-ATF4 pathway and investigate its cytoprotective mechanism. Here, we demonstrated that polysulfide treatment promoted the oligomerization of PERK and PTP1B in neuronal cells using western blotting under nonreducing conditions. We also observed that l-cysteine, a biological source of sulfane sulfur, promoted the oligomerization of PERK and the knockdown of CBS and 3-MST, two sulfane sulfur-producing enzymes, and reduced PERK oligomerization induced by l-cysteine treatment. Furthermore, the band shift assay and LC-MS/MS studies revealed that polysulfides and persulfides induce PTP1B and PERK persulfidation. Additionally, polysulfides promoted eIF2α phosphorylation and ATF4 accumulation in the nucleus, suggesting that polysulfides activate the PERK-eIF2α-ATF4 pathway in neuronal cells. Moreover, polysulfides protected neuronal cells from methylglyoxal-induced toxicity, and this protective effect was reduced when the expression of Sestrin2, regulated by ATF4 activity, was suppressed. This study identified a novel mechanism for the activation of the PERK-eIF2α-ATF4 pathway through persulfidation by polysulfides and persulfides. Interestingly, activation of this pathway overcame the toxicity of methylglyoxal in dependence on Sestrin2 expression. These findings deepen our understanding of neuronal diseases involving ER stress and UPR disturbance and may inspire new therapeutic strategies.

项与 STK24 相关的新闻（医药）

2024-03-04

·精准药物

新型药物靶标

本文将近期药物研发新兴靶标进行汇总，涵盖肿瘤、代谢、呼吸系统等领域，这些靶标一般是近期报道的具有一定治疗潜力的新型靶标，以期为科研人员提供参考。新型靶标的发现是药物研发的关键。本文就近期在国际知名期刊报道的新型药物靶标的研发进展进行汇总（表1），并参考数据库对不同靶标的候选药物研发进展进行阐述。表1：近期报道的新型药物靶标列举Pin1蛋白的SUMOylation（SUMO化修饰）是近年来备受关注的一类蛋白翻译后修饰，高度的蛋白SUMO化促进了结直肠癌、乳腺癌和脑癌等多种肿瘤发展。近期，在Nature Communications上发表了题为“Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells”的文章（Ref 1），其发现Pin1蛋白在胶质瘤干细胞（GSC）中被去泛素化酶USP34稳定而高表达，且Pin1通过催化已知唯一的SUMO E2酶Ubc9来促进GSC中的全局蛋白SUMO化，并揭示了调控Pin1/USP34、Pin1/Ubc9结合的多个激酶，为靶向Pin1蛋白和全局蛋白SUMO化治疗包括胶质瘤在内的癌症提供了多个潜在药物靶标，具有十分重要的基础与转化意义。在该研究中，使用Pin1抑制剂Sulfopin和CDK1抑制剂RO3306联合治疗荷瘤小鼠，有效抑制了GSC中的SUMO1型蛋白SUMO化修饰，减缓了小鼠颅内胶质母细胞瘤（GBM）的生长，极大延长了小鼠生存期。总之，该研究阐明了肿瘤中调控Pin1蛋白稳定性的上游机制，剖析了Pin1上调SUMO1型蛋白SUMO化的下游机制，有助于发展针对GBM和其它受Pin1驱动的恶性肿瘤的治疗新策略。OTUB2肿瘤免疫逃逸给肿瘤的治疗带来了极大障碍。PD-1/PD-L1通路是肿瘤细胞进行免疫逃逸的关键通路。近期，在Nature Communications上发表了题为“Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1”的文章（Ref 2），确定了肿瘤细胞表达的Otubain-2（OTUB2）是抗肿瘤免疫的负调控因子，通过PD-1/PD-L1信号通路在各种人类癌症中发挥作用，并表明OTUB2具有成为肿瘤诊断和治疗靶标的潜力。在该研究中，通过对TCGA数据分析，发现OTUB2与T细胞活化基因表达呈负相关。随后，通过免疫沉淀质谱等方法，发现了OTUB2和PD-L1存在相互作用，其中PD-L1的ICD结构域以及OTUB2酶活部位的第51位半胱氨酸对OTUB2与PD-L1的相互作用至关重要。在机制方面，OTUB2与PD-L1相互作用，并通过干预内质网蛋白降解（ERAD）通路使PD-L1蛋白去泛素化和稳定。总之，该研究揭示了去泛素化酶OTUB2通过去泛素化作用稳定PD-L1从而促进肿瘤免疫逃逸的机制，并提出了利用靶向OTUB2的功能抑制剂来降低肿瘤细胞PD-L1表达水平，增强细胞毒性T细胞抗肿瘤免疫应答的肿瘤治疗策略。STK24丝氨酸/苏氨酸激酶STK24属于Ste20家族的生发中心激酶（GCK）Ⅲ亚家族，主要涉及激活调控多种细胞功能（包括细胞凋亡和细胞迁移）的丝裂原活化蛋白激酶（MAPK）级联反应。近期，在Advanced Science上发表了题为“Protein Kinase STK24 Promotes Tumor Immune Evasion via the AKT-PD-L1 Axis”的文章（Ref 3），其揭示了STK24在通过磷酸化AKT和促进PD-L1表达来协调肿瘤免疫逃逸反应中的关键作用，并且通过STK24抑制有效克服了肿瘤对抗PD-1疗法的内在抵抗。研究发现STK24通过削弱肿瘤免疫力来促进肿瘤发生。在免疫缺陷小鼠中，STK24缺陷对肿瘤形成没有明显影响，但在免疫正常的小鼠中显著阻碍肿瘤生长，并伴随着细胞毒性CD8+T细胞和自然杀伤（NK）细胞在肿瘤组织中的增加浸润。进一步发现，STK24通过磷酸化AKT的一个先前未被发现的Thr21位点来增强肿瘤细胞中PD-L1的表达。STK24缺陷显著提高了抗PD-1免疫治疗的疗效。STK24的表达水平与AKT Thr21磷酸化和PD-L1的表达呈正相关，与CD8+T细胞的浸润和患者的生存结果呈负相关。总之，该研究表明STK24可能是开发更有效的免疫治疗干预措施的潜在靶标。PAK4化疗是治疗晚期非小细胞肺癌（NSCLC）的主要方法，使用顺铂的化疗是一线治疗的主要方法。顺铂通过诱导凋亡直接杀死癌细胞，但长期使用顺铂常常导致耐药。p21活化激酶（PAKs）是一个丝氨酸/苏氨酸（Thr）蛋白激酶家族，与许多致癌信号通路密切相关。PAKs在基因转录、细胞骨架重组、致癌转化、细胞增殖和细胞侵袭等方面发挥调控作用。近期，在Cell Death Discovery上发表了题为“Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress”的文章（Ref 4），其揭示PAK4可能是NSCLC化疗耐药性的一个有价值的治疗靶标。研究数据表明，通过抑制GRP78表达，PAK4敲低可通过调节内质网应激来促进NSCLC对顺铂的敏感性。这为顺铂耐药的机制研究提供新见解。【参考资料】1. 科睿唯安CDDI数据库, 检索日期: 2024年1月23日.2. 生物世界、转化医学网、BioArt、医药观澜、iNature、学术经纬等公开网络资源.声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

免疫疗法