更新于：2024-05-01

Chk1

检测点激酶1

更新于：2024-05-01

基本信息

别名

Cell cycle checkpoint kinase、checkpoint kinase 1、Checkpoint kinase-1

+ [6]

简介

Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:9278511, PubMed:12676583, PubMed:14681206, PubMed:12676925, PubMed:12759351, PubMed:19734889, PubMed:14559997). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:9278511, PubMed:12676583, PubMed:14681206, PubMed:12676925, PubMed:12759351, PubMed:19734889). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:9278511, PubMed:19734889, PubMed:20090422). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758). Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.

关联

项与 Chk1 相关的药物

LY-2880070

靶点

Chk1

作用机制

Chk1抑制剂

在研机构

Esperas Pharma Inc.初创企业 [+2]

原研机构

Eli Lilly & Co.

在研适应症

促纤维增生性小圆细胞瘤 [+11]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

Prexasertib Mesylate Hydrate

普瑞色替

靶点

Chk1 x Chk2

作用机制

Chk1抑制剂 [+1]

在研机构

Acrivon AB [+2]

原研机构

Array BioPharma, Inc.

在研适应症

转移性三阴性乳腺癌 [+8]

非在研适应症

晚期癌症 [+14]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

CCT-245737

靶点

Chk1

作用机制

Chk1抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 Chk1 相关的临床试验

NCT05983523 / Not yet recruiting临床1期

A Phase I Study of PEP07 (Checkpoint Kinase 1 Inhibitor) in Patients With Advanced or Metastatic Solid Tumors

The goal of this clinical trial is To establish the safety profile and determine the dose-limited toxicity (DLT) of PEP07 monotherapy in patients with advanced or metastatic solid tumors. To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of PEP07 monotherapy.
Participants will receive PEP07 administered orally once daily (QD) for 2 consecutive days and 5 days off, every week for 4 weeks until disease progression, intolerable toxicity, confirmed pregnancy, death, consent withdrawal, or other anti-cancer treatment is required, or the Sponsor ends the study, whichever occurs first.

开始日期2023-12-28

申办/合作机构

PharmaEngine, Inc.

NCT05659732 / Recruiting临床1期

A Phase 1b Study of PEP07 (Checkpoint Kinase 1 Inhibitor) in Patients With Advanced Cancer

The goal of this clinical trial is
To assess the safety and tolerability of PEP07 administered orally as a single dose and at escalating dose levels, and, to determine the dose-limiting toxicity (DLT) of study treatment in patients with Acute Myeloid Leukemia (AML) and Mantle Cell Lymphoma (MCL).
To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of PEP07 monotherapy.
Participants will receive PEP07 administered orally once daily (QD) for 2 consecutive days and 5 days off, every week for 4 weeks until disease progression, intolerable toxicity, confirmed pregnancy, death, consent withdrawal, HSCT or other anti-cancer treatment is required, or the Sponsor ends the study, whichever occurs first.

开始日期2023-07-17

申办/合作机构

PharmaEngine, Inc.

NCT05827614 / Recruiting临床1期

An Open-Label, Multicenter, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-355 and BBI-355 in Combination With Select Targeted Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Oncogene Amplifications

BBI-355 is an oral, potent, selective checkpoint kinase 1 (or CHK1) small molecule inhibitor in development as an ecDNA (extrachromosomal DNA) directed therapy (ecDTx). This is a first-in-human, open-label, 3-part, Phase 1/2 study to determine the safety profile and identify the maximum tolerated dose and recommended Phase 2 dose of BBI-355 administered as a single agent or in combination with select therapies.

开始日期2023-03-24

申办/合作机构

Boundless Bio, Inc.初创企业

100 项与 Chk1 相关的临床结果

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100 项与 Chk1 相关的转化医学

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0 项与 Chk1 相关的专利（医药）

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4,093

项与 Chk1 相关的文献（医药）

2024-03-01·Journal of biochemical and molecular toxicology

Bisphenol A regulates bladder cells responses via control of G2/M-phase cell cycle, apoptotic signaling, MAPK pathway, and transcription factor-associated MMP modulation.

Article

作者: Jun-Hui Song ; Byungdoo Hwang ; Solbi Park ; Soobin Kim ; Dong-Ho Kim ; Yung Hyun Choi ; Wun-Jae Kim ; Sung-Kwon Moon

Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, is widely used to produce polycarbonate plastics. The widely used BPA has been detected in human urine samples, raising public anxiety about the detrimental effects of BPA on the bladder. In this study, we explored regulatory mechanisms for the adverse effects of BPA in human bladder BdFC and T24 cells. BPA induced extrinsic and intrinsic apoptosis and G2/M cell cycle arrest caused by the ATM-CHK1/CHK2-CDC25c-CDC2 signaling, which ultimately inhibited the growth of human bladder cells. We also found that BPA decreased the binding activity of AP-1 and NF-κB transcription factors in human bladder cells, which inhibited migration and invasion through matrix metallopeptidase-2 and -9 inactivation. Phosphorylation of MAPKs was implicated with BPA-mediated detrimental effects in human bladder cells. Collectively, our results provide a novel explanation for the underlying molecular mechanisms that BPA induces cytotoxicity in human bladder cells.

2024-02-22·Molecular neurobiology

High Homocysteine-Thiolactone Leads to Reduced MENIN Protein Expression and an Impaired DNA Damage Response: Implications for Neural Tube Defects.

Article

作者: Baoling Bai ; Chunlei Wan ; Zonghui Xiao ; Dan Li ; Lingyun Liu ; Kexin Zhang ; Ting Zhang ; Qin Zhang

DNA damage is associated with hyperhomocysteinemia (HHcy) and neural tube defects (NTDs). Additionally, HHcy is a risk factor for NTDs. Therefore, this study examined whether DNA damage is involved in HHcy-induced NTDs and investigated the underlying pathological mechanisms involved. Embryonic day 9 (E9) mouse neuroectoderm cells (NE4C) and homocysteine-thiolactone (HTL, active metabolite of Hcy)-induced NTD chicken embryos were studied by Western blotting, immunofluorescence. RNA interference or gene overexpression techniques were employed to investigate the impact of Menin expression changes on the DNA damage. Chromatin immunoprecipitation-quantitative polymerase chain reaction was used to investigate the epigenetic regulation of histone modifications. An increase in γH2AX (a DNA damage indicator) was detected in HTL-induced NTD chicken embryos and HTL-treated NE4C, accompanied by dysregulation of phospho-Atr-Chk1-nucleotide excision repair (NER) pathway. Further investigation, based on previous research, revealed that disruption of NER was subject to the epigenetic regulation of low-expressed Menin-H3K4me3. Overexpression of Menin or supplementation with folic acid in HTL-treated NE4C reversed the adverse effects caused by high HTL. Additionally, by overexpressing the Mars gene, we tentatively propose a mechanism whereby HTL regulates Menin expression through H3K79hcy, which subsequently influences H3K4me3 modifications, reflecting an interaction between histone modifications. Finally, in 10 human fetal NTDs with HHcy, we detected a decrease in the expression of Menin-H3K4me3 and disorder in the NER pathway, which to some extent validated our proposed mechanism. The present study demonstrated that the decreased expression of Menin in high HTL downregulated H3K4me3 modifications, further weakening the Atr-Chk1-NER pathway, resulting in the occurrence of NTDs.

2024-02-21·RSC medicinal chemistry

Discovery of 5-trifluoromethyl-2-aminopyrimidine derivatives as potent dual inhibitors of FLT3 and CHK1

Article

作者: Deng, Minjie ; Gao, Yue ; Wang, Peipei ; Du, Wenjing ; Xu, Gaoya ; Li, Jia ; Zhou, Yubo ; Liu, Tao

Here, we discover an FLT3/CHK1 dual inhibitor (30) that exhibits excellent kinase potency and antiproliferative activity against MV4-11 cells. Simultaneously, 30 possesses high selectivity over c-Kit enzyme and low hERG inhibitory ability. Compound 30, meanwhile, overcomes varied resistance in BaF3 cell lines carrying FLT3-TKD and FLT3-ITD mutations. Moreover, 30 demonstrates favorable oral PK properties and kinase selectivity. These conclusions support that compound 30 may be a promising potential FLT3/CHK1 dual agent for further development.

项与 Chk1 相关的新闻（医药）

2024-04-06

·医药观澜

3月，超60款1类新药在中国获批临床（附PDF下载）

▎药明康德内容团队编辑根据中国国家药监局药品审评中心（CDE）官网，在刚刚结束的3月，有超过60款1类新药首次在中国获批临床。按照新注册分类，“1类新药”是指尚未在全球任何国家和地区获批上市的药物，它们也往往代表了药物研发领域的前沿方向。本文中就让我们来看看这些1类新药都有哪些？又有望惠及哪些患者？图片来源：123RF从药物类型来看，3月首次在中国获批临床的1类新药呈现“百花齐放”的状态，涵盖了小分子靶向药、抗体偶联药物（ADC）、单抗、双抗、三抗、核酸药物、细胞与基因疗法、多肽、分子胶、核药等诸多类型。在已披露作用机制的药物中，小分子靶向药占比最多，达30%左右。它们的靶点包括了RXRα、NR2B、KCNQ2/3、CGRP受体、PKR、S1P1、CHK1、RTK、MAT2A、KRAS G12D、IDH1/IDH2等。其次是抗体偶联药物（ADC），有7款。▲3月首次在中国获批临床的1类新药分子类型分布从疾病领域来看，在3月首次在中国获批临床的1类新药中，抗肿瘤药物有近30款，占比超过40%。其次是自身免疫及炎症性疾病，占比超过10%。此外还涵盖了罕见病、神经/精神系统疾病、代谢性疾病、心血管疾病、血液病等疾病领域。▲3月首次在中国获批临床的1类新药疾病领域分布以下将分享部分在3月获批临床的ADC疗法的基本信息，供读者参阅。欲了解更多药物的信息，请扫描下方二维码，即可获得“2024年3月首次在中国获得临床试验默示许可的1类新药”完整PDF文件。AZD9829：一种靶向CD123的抗体与阿斯利康（AstraZeneca）专有的拓扑异构酶1抑制剂（TOP1i）有效载荷连接而成的ADC。该药的主要作用机制是将TOP1i载荷递送到表达CD123的癌细胞中，导致DNA损伤和细胞凋亡。该药在中国获批临床，拟开发治疗CD123阳性恶性血液疾病。JSKN016注射液：康宁杰瑞研发的新一代双抗ADC，可同时靶向HER3和TROP2。JSKN016与肿瘤细胞表面TROP2或者HER3结合后，通过靶点介导的内吞作用进入到溶酶体中，释放出具有细胞毒性的拓扑异构酶I抑制剂 (TOPIi），进而诱导肿瘤细胞死亡。该抑制剂还可以穿透细胞膜，进入到抗原阴性的肿瘤细胞中发挥旁观者效应，两者的叠加作用可以有效抑制肿瘤细胞的生长。该药获批临床的适应症为晚期恶性实体瘤。注射用BL-M05D1：百利天恒全资子公司SystImmune开发的在研一款ADC，采用专有的Claudin18.2特异性抗体开发。由于与Claudin18.2特异性结合，BL-M05D1对包括胃癌在内的表达Claudin18.2的恶性肿瘤具有特异性。该药获批临床的适应症为局部晚期或转移性胃癌或胃食管交界处癌、胰腺癌、结直肠癌等实体瘤。SYS6023：石药集团巨石生物研发的一款单克隆抗体偶联药物，可与肿瘤表面的特异性受体结合。该药在临床前研究中对多种癌症显示出了较好的抗肿瘤作用。本次获批临床的适应症为晚期实体瘤。注射用NC18：诺灵生物自主研发的新型靶向HER2的ADC，采用了独特的Polymer linker和诺灵生物独家的AF-HEA细胞毒素，该组合展现出良好的活性、可控的旁杀效应、更好的抗耐药性。该产品获批临床的适应症为HER2阳性或表达的复发或转移的晚期实体瘤。IBI130：信达生物研发的一款靶向TROP2的ADC，此前已经在澳大利亚开展1/2期临床研究，用于治疗实体瘤。IBI129：信达生物在研的靶向B7-H3的ADC，此前已经登记开展了一项国际多中心1/2期临床试验，针对实体瘤。除了上述药物，3月还有包括CGT、抗体药物、小分子靶向疗法、多肽等在内的其它类型药物首次在中国获批临床，限于篇幅，本文不再一一介绍。希望这些新药后续临床研究顺利进行，早日造福患者！扫描下方二维码，您将可以获取“2024年3月首次在中国获得临床试验默示许可的1类新药”完整PDF文件。参考资料：[1]中国国家药监局药品审评中心（CDE）官网. From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c[2] 各公司官网及新闻稿本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

抗体药物偶联物申请上市基因疗法临床申请核酸药物

2024-04-05

·PRNewswire

BOLD-100 and ATR Inhibitors as a New Avenue for PDAC Targeting at AACR 2024

VANCOUVER, BC, April 5, 2024 /PRNewswire/ -- Bold Therapeutics, a clinical-stage biopharmaceutical company at the forefront of developing innovative metallotherapeutics, has announced that Dr. Do-Youn Oh's group at Seoul National University College of Medicine, Seoul, South Korea, will be presenting at the AACR Annual Meeting, April 5-10, 2024, in San Diego, California on the use of BOLD-100 in combination with ATR (Ataxia telangiectasia and Rad3-related protein serine/threonine kinase) inhibitors as anticancer therapies for the treatment of Pancreatic Ductal Adenocarcinoma (PDAC). Continue Reading Bold Therapeutics announced Dr. Do-Youn Oh’s group at Seoul National University College of Medicine, Seoul, South Korea, will present at the AACR Annual Meeting, April 5-10, 2024, in San Diego, California on the use of BOLD-100 in combination with ATR inhibitors as anticancer therapies for the treatment of Pancreatic Ductal Adenocarcinoma (PDAC). Dr. Do-Youn Oh, MD, PhD, Seoul National University College of Medicine Bold Therapeutics' BOLD-100, a pioneering ruthenium-based small molecule, uniquely acts by (1) targeting GRP78 to modulate the unfolded protein response (UPR) and (2) generating reactive oxygen species (ROS) leading to DNA damage and cell cycle arrest. This dual action triggers cell death across a spectrum of cancer types, including those resistant to current treatments. As a result, BOLD-100 holds promise for significantly enhancing treatment outcomes in a diverse array of both solid and liquid tumors when used alongside a broad range of anticancer treatments, from conventional chemotherapies to cutting-edge targeted therapies and immuno-oncology agents. Our recent presentation at ASCO GI 2024 showcased positive Phase 2 clinical trial results in the treatment of advanced metastatic colorectal cancer (mCRC) in patients previously treated with FOLFOX / CAPOX. The data, highlighting patients treated with a combination of BOLD-100 and FOLFOX, demonstrated notable safety and clinical improvements, bolstering confidence in the therapeutic value of BOLD-100. Dr. Do-Youn Oh's group at Seoul National University College of Medicine, South Korea will be presenting a poster entitled, "Co-downregulation of GRP78 and ATR enhances apoptosis in pancreatic ductal adenocarcinoma," (Poster no. 12, Session: Cellular Stress Responses 1). This work underscores the significant impact of BOLD-100 in inducing GRP78 inhibition, which substantially triggers oxidative stress. Furthermore, when combined with ATR inhibition, this synergy effectively promotes cell death. Key Findings: BOLD-100 elevates ER stress and ROS, leading to activation of the UPR pathway and CHOP-dependent apoptosis, which inhibits PDAC growth; ROS accumulation activates the ATR-CHK1 DNA damage repair pathway, which NAC can abrogate; and The combination of BOLD-100 with the ATR inhibitor AZD6738 exhibits a synergistic effect, suggesting GRP78/ATR dual targeting as a promising therapeutic approach for PDAC. These findings unveil a compelling strategy for combinational targeting to inhibit PDAC growth. "DNA repair mechanisms play a crucial role in maintaining genomic integrity, leading to cell cycle arrest and thereby preventing the uncontrolled growth and progression of cancer cells. Our in-vitro and in-vivo findings indicate that combining BOLD-100 with ATR inhibition results in synthetic lethality against highly aggressive Pancreatic Ductal Adenocarcinoma. We are eager to delve deeper into this research path and its potential clinical utility," stated Dr. Oh. Mark Bazett, Sr Director, Preclinical Development at Bold Therapeutics added, "BOLD-100 has already demonstrated remarkable safety and efficacy in the treatment of metastatic colorectal cancer (mCRC). Diverging from the path of targeted therapies, BOLD-100's unique multi-modal mechanism-of-action opens avenues for potent combination therapies designed to tackle some of the most difficult-to-treat cancers including those resistant to standard treatments. The synergistic combination identified by Dr. Oh's group holds particular promise, and we look forward to further exploring this potential." Jim Pankovich, EVP, Clinical Development at Bold Therapeutics, and Mark Bazett, Sr Director, Preclinical Development at Bold Therapeutics, will also be attending the 2024 AACR Annual Meeting in San Diego and are available for in-person discussions related to BOLD-100. For additional details, visit Bold Therapeutics' website at or the AACR conference site at Contact: E. Russell McAllister, CEO [email protected] +1 (604) 262-9899 SOURCE Bold Therapeutics Inc.

临床2期临床结果AACR会议

2024-04-04

·生物谷

热敏miRNA和冷诱导RNA结合蛋白可调节癌症干性，为热疗抵抗提供新靶点

该研究首先证实了热疗可以显著降低鼻咽癌（NPC）细胞的干性，而热疗和冬凌草甲素（中药冬凌草的主要活性成分）联合治疗极大增强了对NPC细胞和癌症干细胞（CSC）样细胞的杀伤作用。以我国南方好发的鼻咽癌（NPC）作为癌症研究对象，南方医科大学肿瘤研究所和附属广东省人民医院、南方医院以及南方科技大学第二附属医院（深圳市第三人民医院）等机构的研究人员在 Journal of Experimental & Clinical Cancer Research 期刊发表了题为：ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia 的研究论文。该研究首次报道了冷诱导RNA结合蛋白（Cirbp）可促进癌细胞DNA损伤修复致使热疗抵抗。ThermomiR-377-3p（热敏miRNA-377-3p）及其靶基因Cirbp是热敏的重要调节因子，有望成为癌症治疗有价值的新靶点。该研究首先证实了热疗可以显著降低鼻咽癌（NPC）细胞的干性，而热疗和冬凌草甲素（中药冬凌草的主要活性成分）联合治疗极大增强了对NPC细胞和癌症干细胞（CSC）样细胞的杀伤作用。此外，热疗显著提高了放疗抵抗的NPC细胞和CSC样细胞对放疗的敏感性。研究团队进而发现，热疗显著抑制鼻咽癌（NPC）细胞和裸鼠移植瘤中冷诱导RNA结合蛋白（Cirbp）的表达。Cirbp沉默可大为增强热疗对NPC细胞和CSC样细胞的杀伤作用，而Cirbp过表达作用则相反，提示Cirbp可诱导热疗抵抗。在体外实验中，ThermomiR-377-3p通过直接抑制Cirbp的表达来提高NPC细胞和CSC样细胞对热疗的敏感性。更重要的是，Cirbp沉默明显增强了体内移植瘤对热疗的敏感性，其过表达作用则完全相反。最后，研究团队从机制上进行了深入分析，结果发现，Cirbp沉默通过使ATM-Chk2和ATR-Chk1通路失活而抑制DNA损伤修复，导致癌细胞干性减少和死亡增加；相反，Cirbp过表达促进癌细胞DNA损伤修复、干性增加以及减少细胞凋亡，从而导致热疗抵抗。 Cirbp介导的对热疗抵抗和敏感信号调控机制林桃燕、贾俊双、罗伟仁和林晓琳等为该论文的共同第一作者，孙妍、肖东、黄文华和赵冰夏为论文共同通讯作者。该研究工作得到了国家自然科学基金委面上项目、广东省自然科学基金面上项目以及深圳市自然科学基金重点/面上项目等支持。