更新于：2024-09-19

MARK3

更新于：2024-09-19

基本信息

别名

C-TAK1、Cdc25C-associated protein kinase 1、CTAK1

+ [11]

简介

Serine/threonine-protein kinase (PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216' (PubMed:12941695). Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). Phosphorylates PKP2 and KSR1 (PubMed:12941695).

关联

100 项与 MARK3 相关的临床结果

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100 项与 MARK3 相关的转化医学

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0 项与 MARK3 相关的专利（医药）

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929

项与 MARK3 相关的文献（医药）

2024-10-15·Rapid Communications in Mass Spectrometry

Characterization of metabolic features and potential anti‐osteoporosis mechanism of pinoresinol diglucoside using metabolite profiling and network pharmacology

Article

作者: Li, Meng‐Yin ; Zeng, Jian‐Bin ; Shi, Wei ; Zhang, Feng‐Xiang ; Tu, Xin‐Pu ; Liu, Jian‐Hang ; Liu, Cheng‐Jun ; Ruan, Yan‐Jie ; Chen, Zi‐Hao ; Wu, Si‐Xian

RationaleEucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti‐osteoporotic mechanism are still unclear, restricting its development and application.MethodsUltra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti‐osteoporosis targets and mechanism were predicted using network pharmacology.ResultsA total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan‐ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K‐Akt signaling pathway, estrogen signaling pathway, and so on.ConclusionsThis study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti‐osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis.

2024-07-01·Biochemical and Biophysical Research Communications

Dysfunction of Avo3, an essential component of target of rapamycin complex 2, induces ubiquitin-proteasome-dependent downregulation of Avo2 in Saccharomyces cerevisiae

Article

作者: Chen, Pao-Kuang ; Chen, Mei-Yu ; Chou, Yu-Wen ; Chang, Yu-Jung

The ubiquitin-proteasome system (UPS) plays a key role in maintaining cellular protein homeostasis and participates in modulating various cellular functions. Target of rapamycin (TOR), a highly conserved Ser/Thr kinase found across species from yeasts to humans, forms two multi-protein complexes, TORC1 and TORC2, to orchestrate cellular processes crucial for optimal growth, survival, and stress responses. While UPS-mediated regulation of mammalian TOR complexes has been documented, the ubiquitination of yeast TOR complexes remains largely unexplored. Here we report a functional interplay between the UPS and TORC2 in Saccharomyces cerevisiae. Using avo3-2^ts, a temperature-sensitive mutant of the essential TORC2 component Avo3 exhibiting TORC2 defects at restrictive temperatures, we obtained evidence for UPS-dependent protein degradation and downregulation of the TORC2 component Avo2. Our results established the involvement of the E3 ubiquitin ligase Ubr1 and its catalytic activity in mediating Avo2 degradation in cells with defective Avo3. Coimmunoprecipitation revealed the interaction between Avo2 and Ubr1, indicating Avo2 as a potential substrate of Ubr1. Furthermore, depleting Ubr1 rescued the growth of avo3-2^ts cells at restrictive temperatures, suggesting an essential role of Avo2 in sustaining cell viability under heat stress and/or TORC2 dysfunction. This study uncovers a role of UPS in yeast TORC2 regulation, highlighting the impact of protein degradation control on cellular signaling.

2024-07-01·Molecular Neurobiology

Mendelian Randomization Identifies Genetically Supported Drug Targets for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Article

作者: Li, Mao ; Yang, Fei ; Pang, Xinyuan ; Du, RongRong ; Huang, Xusheng ; Zhu, Yahui ; Wang, Hongfen ; Bai, Jiongming

Currently, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have no effective treatments. Drug repurposing offers a rapid method to meet therapeutic need for ALS and FTD. To identify therapeutic targets associated with ALS and FTD, Mendelian randomization (MR) analysis and colocalization were performed. Genetic instruments were based on transcriptomic and proteomic data for 422 actionable proteins targeted by approved drugs or clinical drug candidates. The publicly available ALS GWAS summary data (including a total of 20,806 ALS cases and 59,804 controls) and FTD GWAS summary data (including a total of 2154 patients with FTD and 4308 controls) were used. Using cis-expression quantitative trait loci and cis-protein quantitative trait loci genetic instruments, we identified several drug targets for repurposing (ALS: MARK3, false-discovery rate (FDR) = 0.043; LTBR, FDR = 0.068) (FTD: HLA-DRB1, FDR = 0.083; ADH5, FDR = 0.056). Our MR study analyzed the actionable druggable proteins and provided potential therapeutic targets for ALS and FTD. Future studies should further elucidate the underlying mechanism of corresponding drug targets in the pathogenesis of ALS and FTD.

项与 MARK3 相关的新闻（医药）

2023-12-22

·生物谷

Clin Epigenet：慢性偏头痛研究或能揭示降低机体偏头痛频率的特殊遗传学机制

来自昆士兰理工大学等机构的科学家们通过研究揭示了慢性偏头痛患者在逐渐停用偏头痛药物后机体偏头痛频率降低背后的生物学机制。慢性偏头痛是一种高度致残的亚型偏头痛，其影响着近2%的普通人群，理解偏头痛的慢性化对于开发更好的疗法和预防性策略至关重要，偏头痛慢性化的一种重要因素就是急性头痛药物的过度使用，然而，发作性偏头痛转化为慢性偏头痛背后的分子机制，目前研究人员尚未阐明。近日，一篇发表在国际杂志Clinical Epigenetics上题为“Alterations in DNA methylation associate with reduced migraine and headache days after medication withdrawal treatment in chronic migraine patients: a longitudinal study”的研究报告中，来自昆士兰理工大学等机构的科学家们通过研究揭示了慢性偏头痛患者在逐渐停用偏头痛药物后机体偏头痛频率降低背后的生物学机制。文章中，研究人员揭示了他们如何发现从发作性偏头痛到慢性偏头痛转变过程中所涉及的两个基因的表观遗传学改变。研究者表示，慢性偏头痛是大约2%的普通人群所面临的主要头痛问题；研究者Divya Mehta说道，过度使用缓解急性头痛和其它药物是慢性偏头痛发生发展和维持的一个重要因素。如果患者每月15天或更多的时间会头痛，且会持续3个月或更长时间，其中有8天符合偏头痛的标准，那么研究人员就将这种偏头痛归类为慢性偏头痛，因此这或许是一种高度致残的偏头痛类型。如今研究人员开始理解偏头痛慢性化的过程（即某些偏头痛患者的疾病发作越来越频繁），以及如何逆转这一过程。研究人员调查了DNA甲基化的纵向改变，DNA甲基化是一种表观遗传学修饰，是为了对包括治疗性药物在内的环境因素产生反应而将在DNA分子上添加化学标签，从而就能实现基因的开启或关闭。慢性偏头痛研究或能揭示降低机体偏头痛频率的特殊遗传学机制。图片来源：Clinical Epigenetics (2023). DOI:10.1186/s13148-023-01604-8 文章中，研究人员对慢性偏头痛患者在药物疗法治疗开始时和停药12周后机体的血液进行采集并分析，Sutherland博士说道，我们让患者记录其头痛日志，并将每月的头痛和偏头痛天数减少50%以上的患者（应答者）与无应答者进行比较，从而识别出与其对疗法产生反应相关的DNA甲基化改变。在所有患者中，59.8%的患者在12周的停药期结束时又复发成为发作性偏头痛患者。而且研究人员发现，HDAC4基因的表观遗传学改变与急性药物停药后头痛天数的平均减少有关，DNA甲基化水平的降低与头痛天数的减少有一定关联。其次，研究者发现，MARK3基因内的DNA甲基化与偏头痛天数的平均减少有关；MARK3基因在基线时的DNA甲基化水平较低或与每月偏头痛天数减少有关，且其被发现是一种预测患者对疗法产生反应的特殊生物标志物。这些研究发现具有重大的临床意义，因为其能揭示这些基因或许能作为偏头痛的新型治疗性靶点。综上，本文研究结果表明，与疗法反应相关的HDAC4的DNA甲基化水平的纵向降低，以及基线MARK3的DNA甲基化或能作为指示偏头痛患者对疗法产生反应的早期生物标志物，从而就为揭示染色质结构和突触可塑性相关通路在偏头痛慢性化中的重要作用提供了一定的支持，并引入了HDAC4和MARK3作为新型的治疗性靶点。（生物谷Bioon.com）原始出处： Mehta, D., de Boer, I., Sutherland, H.G. et al. Alterations in DNA methylation associate with reduced migraine and headache days after medication withdrawal treatment in chronic migraine patients: a longitudinal study. Clin Epigenet 15, 190 (2023). doi：10.1186/s13148-023-01604-8