更新于：2024-11-01

CUL3

更新于：2024-11-01

基本信息

别名

CUL-3、CUL3、cullin 3

+ [2]

简介

Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KLHL25) ubiquitin ligase complex is also involved in lipid synthesis by mediating ubiquitination and degradation of ACLY (PubMed:27664236). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and proteasomal degradation of TIAM1 (PubMed:25684205). By controlling the ubiquitination of that RAC1 guanine exchange factors (GEF), regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205).

关联

项与 CUL3 相关的药物

VVD-065

靶点

CUL3 x KEAP1 x Nrf2

作用机制

CUL3调节剂 [+2]

在研机构

Vividion Therapeutics, Inc.

原研机构

Vividion Therapeutics, 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 CUL3 相关的临床结果

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100 项与 CUL3 相关的转化医学

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0 项与 CUL3 相关的专利（医药）

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1,017

项与 CUL3 相关的文献（医药）

2024-12-31·International Journal of Hyperthermia

Hyperthermia and cisplatin combination therapy promotes caspase-8 accumulation and activation to enhance apoptosis and pyroptosis in cancer cells

Article

作者: Peng, Yatu ; Wang, Yue ; Zi, Guanghui ; Peng, Baowei ; Chen, Jin

BACKGROUNDHyperthermia can play a synergistic role with chemotherapy in combination therapy. Although the association between caspase activation, apoptosis, and pyroptosis have been published for both cisplatin (CDDP) and hyperthermia therapies independently, the interactions between these molecular pathways in combination therapy are unknown. The present study aimed to investigate the possible interactions between caspase 8 activation, apoptosis, and pyroptosis in combination therapy.METHODSCells were treated with CDDP (15 µg/ml), followed by hyperthermia at optimized temperature (42.5 °C) in water-bath. After combination therapy, cell viability was analyzed by CCK-8, and cell death was analyzed by Annexin-V-FITC/PI and caspases activation. Immuno-staining and co-immuno-precipitation were used to examine the interaction between p62 and caspase-8. Pyroptosis was investigated by western blotting and transmission electron microscopy. E3 ligase Cullin 3 was knockdown by siRNA. In addition, caspase-8 activation was modulated by CRISPR-Cas9 gene-editing or pharmacological inhibition.RESULTSCombination therapy promoted K63-linked polyubiquitination of caspase-8 and cellular accumulation of caspase-8. In turn, polyubiquitinated caspase-8 interacted with p62 and led to the activation of caspase-3. Knockdown of the E3 ligase Cullin 3 by siRNA reduced caspase-8 polyubiquitination and activation. In addition, combination therapy induced release of the pore-forming N-terminus from gasdermins and promoted pyroptosis along with caspase-8 accumulation and activation. Knockdown of caspase-8 by CRISPR/Cas9 based gene editing reduced the sensitivity of tumor cells to apoptosis and pyroptosis.CONCLUSIONSOur study presented a novel mechanism in which hyperthermia synergized with chemotherapy in promoting apoptosis and pyroptosis in a caspase-8 dependent manner.

2024-11-01·Life Sciences

KLHL20 and its role in cell homeostasis: A new perspective and therapeutic potential

Review

作者: Ramagoma, Rolivhuwa Bishop ; Makgoo, Lilian ; Mbita, Zukile

Ubiquitin ligases are proteins with the ability to trigger non-degradative signaling or proteasomal destruction by attracting substrates and facilitating ubiquitin transfer onto target proteins. Over the years, there has been a continuous discovery of new ubiquitin ligases, and Kelch-like protein 20 (KLHL20) is one of the most recent discoveries that have several biological roles which include its role in ubiquitin ligase activities. KLHL20 binds as a substrate component of ubiquitin ligase Cullin3 (Cul3). Several substrates for ubiquitin ligases (KLHL20 based) have been reported, these include Unc-51 Like Autophagy Activating Kinase 1 (ULK1), promyelocytic leukemia (PML), and Death Associated Protein Kinase 1 (DAPK1). KLHL20 shows multiple cell functions linked to several human diseases through ubiquitination of these substrates. Current literature shows that KLHL20 ubiquitin ligase regulates malignancies in humans and also suggests how important it is to develop regulating agents for tumour-suppressive KLHL20 to prevent tumourigenesis, Recent research has highlighted its potential therapeutic implications in several areas. In oncology, KLHL20's regulatory role in protein degradation pathways suggests that its targeting could offer novel strategies for cancer treatment by modulating the stability of proteins involved in tumour growth and survival. In neurodegenerative diseases, KLHL20's function in maintaining protein homeostasis positions it as a potential target for therapies aimed at managing protein aggregation and cellular stress. Here, we review the functions of KLHL20 during the carcinogenesis process, looking at its role in cancer progression, and regulation of ubiquitination events mediated by KLHL20 in human cancers, as well as its potential therapeutic interventions.

2024-11-01·Hypertension

Prevalence of Hyperkalemia and Familial Hyperkalemic Hypertension in 5100 Patients Referred to a Tertiary Hypertension Unit

Article

作者: Pasini, Barbara ; Rabbia, Franco ; Tetti, Martina ; Crisetti, Annalisa ; Monticone, Silvia ; Jeunemaitre, Xavier ; Hureaux, Marguerite ; Burrello, Jacopo ; Clauser, Eric ; Veglio, Franco ; Billon, Clarisse ; Mulatero, Paolo

BACKGROUND:Hyperkalemia is a frequent electrolyte alteration whose prevalence varies widely, depending on the adopted cutoff, the setting (inpatients versus outpatients), and the characteristics of the study population. Familial hyperkalemic hypertension (FHH) is a rare cause of hypertension, hyperkalemia, and hyperchloremic metabolic acidosis.METHODS: In this retrospective observational study, we investigated the prevalence of hyperkalemia (serum K + >5.2 mmol/L on 2 repeated measurements) in 5100 referred patients affected by arterial hypertension, the potential causes, and the associated cardiovascular risk profile. RESULTS: Overall, 374 (7.3%) patients had hyperkalemia. This was associated with drugs known to increase K + levels (74.6%), chronic kidney disease (33.7%), or both (24.3%). Among the 60 patients with unexplained hyperkalemia, 3 displayed a clinical and biochemical phenotype suggestive of FHH that was genetically confirmed in 2 of them (0.04% in the entire cohort). FHH prevalence rose to 3.3% in patients with unexplained hyperkalemia and up to 29% (2/7) if they had serum K + >5.8 mmol/L. The genetic cause of FHH was a missense variant affecting the acidic motif of WNK1 in 1 family and a rare CUL3 splicing variant, whose functional significance was confirmed by a minigene assay, in another. Finally, we observed a significant association between hyperkalemia and the occurrence of cardiovascular events, metabolic syndrome, and organ damage, independent of potential confounding factors. CONCLUSIONS:The identification of hyperkalemia in patients with hypertension has prognostic implications. A timely diagnosis of FHH is important for effective management of hypertension, electrolyte imbalance correction with tailored treatment, and genetic counseling.

项与 CUL3 相关的新闻（医药）

2024-02-28

·今日头条

关键调控因子！中国医科大学等团队发现癌症免疫检查点阻断治疗最新靶点

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：免疫治疗已成为一线癌症治疗的重要策略。 2月27日，中国医科大学和中国科学院研究团队在期刊《Cell Death & Disease》上在线发表题为“KEAP1 promotes anti-tumor immunity by inhibiting PD-L1 expression in NSCLC”的研究论文，研究揭示了PD-L1降解机制以及NSCLC如何通过KEAP1-PD-L1信号进行免疫逃逸。研究表明，KEAP1激动剂可能是一种潜在的临床药物，可以增强抗肿瘤免疫并改善NSCLC的免疫治疗。研究结果强调了KEAP1作为癌症免疫检查点阻断治疗的一个有希望的靶点。 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-06563-3 研究背景 01 非小细胞肺癌（NSCLC）占据所有肺癌病例的85％，仍然对人类生命构成重大威胁，具有较高的发病率和死亡率。尽管NSCLC存在多种治疗选择，包括放疗、化疗和靶向治疗，但由于药物耐药性和有害副作用的限制，治疗效果有限。因此，源于对肿瘤免疫生物学更深入理解的免疫治疗的出现，成为对抗非小细胞肺癌的一个有希望的突破。免疫治疗已成为一线癌症治疗的重要策略。在非小细胞肺癌（NSCLC）中，PD-L1的表达诱导免疫抑制效应，保护癌细胞免受免疫清除，从而将PD-L1确定为免疫治疗的重要靶点。然而，PD-L1在肺癌中的调控机制和功能知之甚少。 KEAP1是基于Cullin 3的E3泛素连接酶的适配子亚基，在包括代谢重编程、铁死亡、细胞周期和放疗耐药等多种生物过程中发挥重要作用。癌症基因组测序研究表明，大约20％的腺癌和鳞状肺癌存在KEAP1突变。KEAP1突变与肺癌的进展、治疗耐药性和患者生存率较低相关。因此，KEAP1在肺癌进展中扮演重要角色，然而其在免疫治疗中的关系和分子机制尚未完全理解。研究发现 02 在这项研究中，研究人员揭示了KEAP1在通过介导ICB抑制NSCLC进展中先前未被发现的分子机制。研究人员发现KEAP1直接与PD-L1相互作用，随后通过泛素化PD-L1进行蛋白酶体降解来降低 PD-L1 的表达。这种降解增加了CD8+T细胞的数量，从而增强了免疫治疗的有效性。此外，研究人员在临床样本中发现KEAP1与PD-L1之间存在负相关，它们的不同表达与预后相关。研究发现表明KEAP1可能成为抑制NSCLC进展的抗PD-L1免疫治疗的潜在靶点。研究结论 03 综上所述，研究揭示了PD-L1降解机制以及NSCLC如何通过KEAP1-PD-L1信号进行免疫逃逸。研究表明，KEAP1激动剂可能是一种潜在的临床药物，可以增强抗肿瘤免疫并改善NSCLC的免疫治疗。研究结果强调了KEAP1作为癌症免疫检查点阻断治疗的一个有希望的靶点。参考资料： https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-06563-3 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！点击对应文字查看详情

免疫疗法

2024-01-14

·生物制品圈

澳门大学邓初夏团队发布可实现癌症治疗“双重疗效”的新方法

导读：肝内胆管癌（ICC）是原发性肝癌中第二常见的恶性肿瘤，总体发病率增加，预后不良。ICC的瘤间和瘤内异质性使得很难找到有效的药物治疗。因此，鉴定诱导ICC形成和进展的抑癌基因和癌基因至关重要。2014年1月11日，澳门大学邓初夏教授团队在期刊《Cell Death & Disease》上发表题为“The heterogeneity of signaling pathways and drug responses in intrahepatic cholangiocarcinoma with distinct genetic mutations”的研究论文，我们的研究研究数据提供了SPC小鼠的ICC模型。通过HTV将CRISPR文库引入小鼠肝脏，我们筛选了在4个月内加速ICC形成的基因。我们分析了不同基因突变调控的信号转导变化，并为ICC患者提供了潜在的药物治疗策略。https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-023-06406-7研究背景 01 除肝细胞癌（HCC）外，胆管癌（CC）占所有原发性肝癌的10-15%，近年来其总体发病率和死亡率有所上升。CC 是一种胆道上皮肿瘤，根据其解剖部位分为三种亚型：肝内 CC （ICC）、肺门周围 CC （PCC）或远端 CC（DCC）。ICC 位于肝内二级胆管的外围，而 PCC 和 DCC 都位于肝外。混合型HCC-ICC肿瘤具有HCC和ICC的特征，表现为侵袭性肿瘤生长和预后不良。ICC是恶性肿瘤，大多数患者在晚期被诊断出来。ICC在基因组和表观遗传学水平上的瘤间异质性使得很难找到有效的治疗方法。确定ICC形成和进展的复杂机制对于开发新的治疗策略至关重要。许多研究使用综合分析工具揭示了 ICC 的遗传和表观遗传变化。关键调节因子已被证明在 CC 中发生突变，并且与不同的信号通路有关。然而，在基因组改变的患者中，大多数鉴定出的基因具有低频率（<5%），这表明其中许多可能是 ICC 形成和进展过程中的突变而不是驱动突变。然而，在对 200 个人类 CC 标本的基因组分析中，大多数（61.5%）没有显示任何已知的突变，这表明许多癌症驱动突变仍未被发现。研究设计 02 为了确定加速ICC形成的其他驱动因素，我们之前在SPC小鼠中进行了CRISPR / Cas9介导的靶向20,611个基因的全基因组筛选，并将Cul3鉴定为肿瘤抑制因子，其破坏通过诱导肝脏炎症来加速ICC的形成。除了 Cul3 之外，我们的分析还检测到许多其他基因的 sgRNA，这些基因以高频率出现与 ICC 形成相关。在这项研究中，我们进一步分析了我们的顶级候选基因，发现 Trp53、Fbxw7、Inppl1 或 Tgfbr2 的缺陷可以显著增强 SPC 小鼠的 ICC 形成，并且这些基因与几种不同的信号通路相关。我们还对与这些突变相关的ICC衍生类器官进行了高通量药物筛选，为其治疗提供了潜在的治疗策略。研究结果 03 我们的研究确定了在具有不同基因突变的ICC肿瘤中调节的不同信号通路。先前对临床样本进行基因组分析的研究确定了ICC的炎症和增殖类别。结果表明，Trp53、Fbxw7、Inppl1和Tgfbr2突变增强了ICC细胞增殖。Cul3突变似乎会诱导免疫环境变化，从而促进肿瘤形成。增殖类通常显示经典致癌通路的富集，包括 RTK、VEGF、PDGF、RAS-MAPK、PI3K-AKT-mTOR 和 WNT-β-catenin 信号通路。我们的研究确定 FGFR 和 VEGF 通路上调。对于下游通路，由于我们的小鼠模型包含Pten突变背景，进一步的基因突变增强了PI3K信号通路，这可能是由于Fgfr、Vegfr或Igfr的信号转导升高。这些结果表明，PI3K是ICC中激活的主要信号通路。炎症类表现出增强的免疫反应相关通路。在 Fbxw7 突变肿瘤中，许多细胞因子和趋化因子上调，关键的细胞因子转导 Stat 家族也过表达。此外，Fbxw7突变肿瘤对免疫检查点抑制剂反应良好，表明Fbxw7缺陷可能诱导严重的免疫反应，从而加速肿瘤的形成和生长。已鉴定的基因突变在体外和体内促进癌症进展综上所述，使用SPC小鼠模型，结果验证了Trp53、Fbxw7、Inppl1、Tgfbr2和Cul3是ICC的抑癌基因。然而，这些基因启动ICC形成并诱导免疫微环境变化的详细机制需要进一步阐明。在这里，我们分析了受这些基因突变调控的多种信号通路，并研究了多种药物反应，为ICC肿瘤的新治疗策略提供了建议。参考资料：https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-023-06406-7小编收集了254份参会药企在2024年JPM上的报告材料，以供业内参考，向【生物制品圈】公众号消息对话框内发送「2024JPM」即可获取下载2021-2024年四年JPM学习资料。资源清单识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

临床研究基因疗法

2023-11-24

·生物谷

Mol Cell｜北京大学魏文胜团队实现人类蛋白质组中赖氨酸位点的功能解码

氨基酸作为构成蛋白质的基本单位，对于蛋白质的结构和功能至关重要，而其变化也与多种疾病的发生发展密切相关。尽管目前利用碱基编辑等技术[1,2]可以在基因组中实现碱基替换进而改变密码子，产生内源氨基酸的突变，但在全蛋白质组范围内对特定氨基酸残基进行系统性的功能分析仍然面临挑战。2023年11月22日，北京大学魏文胜团队在Molecular Cell杂志在线发表了题为“Unbiased interrogation of functional lysine residues in human proteome”的研究论文。该研究采用腺嘌呤碱基编辑工具，建立了一种在全蛋白质组范围内筛选功能性氨基酸位点的策略，并通过细胞适应性筛选，获得了蛋白质组功能性赖氨酸位点的图谱。在人类蛋白质组众多的氨基酸残基中，研究者首先关注了赖氨酸。赖氨酸残基携带正电荷，在蛋白质的结构、与其他分子的相互作用等方面发挥着重要作用，同时也是多种蛋白质翻译后修饰（如泛素化、乙酰化、甲基化）的重要受体氨基酸残基。赖氨酸的密码子为5’-AAA或5’-AAG，利用腺嘌呤编辑器（Adenine base editors, ABEs）对其密码子进行编辑，可以实现赖氨酸的定向突变（图1）。图1 赖氨酸定向突变示意图该研究利用ABEmax系统在人视网膜色素上皮细胞系RPE1中构建了靶向赖氨酸位点的sgRNA文库[3]，包含约30万条sgRNA，覆盖了85%的编码基因、85%的蛋白质以及35%的赖氨酸密码子。为提高筛选质量并大幅缩减建库所需细胞数量，研究者结合团队前期建立的iBAR策略进行了细胞适应性筛选[4]，最终获得了1572个促进或抑制细胞存活的赖氨酸突变位点。基于课题组前期在RPE1细胞系中进行的基因敲除筛选结果[5]，研究者将赖氨酸位点的得分映射到其所在基因上，形成了基因（蛋白）-赖氨酸位点的功能性图谱（图2）。值得注意的是，大量赖氨酸位点的突变导致细胞表现出与相应基因敲除不同的细胞适应性表型。在这些突变位点中，有805个位点突变后会抑制细胞存活，然而对应的基因敲除却未对细胞存活产生影响或促进细胞存活。通过对国际癌症基因组联盟数据库（ICGC）的数据挖掘，研究者鉴定了若干具有临床意义的赖氨酸突变位点，包括已有报道的TP53-K120、BRAF-K601、PTEN-K13等位点，然而大多数赖氨酸位点的功能仍不为人知。图2 两种筛选结果对比图在正向富集的赖氨酸位点中，研究者发现了一个以CUL3为核心的调控网络。CUL3是泛素化复合物（cullin-RING ligases，CRLs）中的重要成员。该研究筛选到位于其骨架蛋白、接头蛋白、激活蛋白、底物蛋白多个赖氨酸位点（图3）。通过亲和纯化-质谱等方法，研究者发现CUL3-K638E能够显著削弱CUL3和去nedd化复合物（COP9 signalosome，CSN）的结合，导致其持续处于nedd化状态而最终降低了稳定性。图3 CUL3 CRLs复合物最终，研究者将关注点聚焦在CUL3的接头蛋白KCTD10的K171位点上，该位点在一名乳腺癌患者体内检测到了突变（K171E）。通过一系列实验，研究者证实KCTD10-K171能够发生乙酰化修饰，并通过调控细胞周期蛋白TPX2和INCENP的蛋白稳态来控制下游信号通路，确保细胞周期正常进行。KCTD10-K171的突变可能导致细胞周期蛋白无法正常降解，从而引起细胞过度增殖。该位点可能成为潜在的癌症标志突变，有助于癌症的诊断和预后，并为新药研发提供了指导。总的来说，本研究利用碱基编辑技术成功建立了高通量的氨基酸精度功能性筛选方法，为系统性研究蛋白质功能和调控机制提供了新的有效手段。同时，所得到的氨基酸精度的蛋白质功能性大数据为更深入地理解蛋白质调控机制，尤其是翻译后修饰机制，提供了有力的依据（图4）。图4 总结图北京大学魏文胜课题组博士后宝颖、博士研究生潘倩和已毕业的许萍博士和刘志恒博士为论文的共同第一作者，魏文胜教授和副研究员周卓（现为中国医学科学院系统医学研究院/苏州系统医学研究所研究员）为论文的共同通讯作者。该研究获得了国家重点研发计划、国家自然科学基金、北京市科委生物医学前沿创新推进项目、中国医学科学院医学与健康科技创新工程、北大-清华生命科学联合中心、昌平实验室、重大疾病共性机制研究全国重点实验室等的支持。原文链接：https://linkinghub-elsevier-com.libproxy1.nus.edu.sg/retrieve/pii/S1097276523008705本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！