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1.
Int J Mol Sci ; 25(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-39000015

RESUMEN

Vegetables, as indispensable non-staple foods in people's daily diet, provide a variety of essential vitamins, minerals, and other nutrients, as well as special phytochemicals, which are recognized as functional components for human nutritional balance or medicinal purposes [...].


Asunto(s)
Genómica , Verduras , Verduras/genética , Genómica/métodos , Humanos , Genoma de Planta , Fitoquímicos
2.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2290-2298, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38812129

RESUMEN

Ligustilide is the main active component of the volatile oil from Angelica sinensis and Ligusticum chuanxiong in the Umbelliferae family. It is a phthalein compound with anti-inflammatory, analgesic, antioxidant, anti-tumor, anti-atherosclerosis, neuroprotective, and other pharmacological effects. It can improve the permeability of the blood-brain barrier and has important potential in the treatment of neurodegenerative diseases and other nervous system diseases, such as Alzheimer's disease, ischemic stroke, Parkinson's disease, vascular dementia, and depression. Therefore, the mechanism of ligustilide in the treatment of nervous system diseases was summarized to provide a reference for drug development and clinical application.


Asunto(s)
4-Butirolactona , Enfermedades del Sistema Nervioso , Humanos , Animales , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , 4-Butirolactona/química , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico
3.
Plant Physiol ; 195(2): 970-985, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38478469

RESUMEN

The Xishuangbanna (XIS) cucumber (Cucumis sativus var. xishuangbannanesis) is a semiwild variety that has many distinct agronomic traits. Here, long reads generated by Nanopore sequencing technology helped assembling a high-quality genome (contig N50 = 8.7 Mb) of landrace XIS49. A total of 10,036 structural/sequence variations (SVs) were identified when comparing with Chinese Long (CL), and known SVs controlling spines, tubercles, and carpel number were confirmed in XIS49 genome. Two QTLs of hypocotyl elongation under low light, SH3.1 and SH6.1, were fine-mapped using introgression lines (donor parent, XIS49; recurrent parent, CL). SH3.1 encodes a red-light receptor Phytochrome B (PhyB, CsaV3_3G015190). A ∼4 kb region with large deletion and highly divergent regions (HDRs) were identified in the promoter of the PhyB gene in XIS49. Loss of function of this PhyB caused a super-long hypocotyl phenotype. SH6.1 encodes a CCCH-type zinc finger protein FRIGIDA-ESSENTIAL LIKE (FEL, CsaV3_6G050300). FEL negatively regulated hypocotyl elongation but it was transcriptionally suppressed by long terminal repeats retrotransposon insertion in CL cucumber. Mechanistically, FEL physically binds to the promoter of CONSTITUTIVE PHOTOMORPHOGENIC 1a (COP1a), regulating the expression of COP1a and the downstream hypocotyl elongation. These above results demonstrate the genetic mechanism of cucumber hypocotyl elongation under low light.


Asunto(s)
Cucumis sativus , Genoma de Planta , Hipocótilo , Sitios de Carácter Cuantitativo , Hipocótilo/crecimiento & desarrollo , Hipocótilo/genética , Cucumis sativus/genética , Cucumis sativus/crecimiento & desarrollo , Sitios de Carácter Cuantitativo/genética , Fitocromo B/genética , Fitocromo B/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Luz
4.
Eur J Pharmacol ; 952: 175752, 2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37164118

RESUMEN

Although rat sarcoma viral oncogene homolog (RAS) mutations occur in about 30% of solid tumors, targeting RAS mutations other than KRAS-G12C is still challenging. As an alternative approach, developing inhibitors targeting RAF, the downstream effector of RAS signaling, is currently one of the main strategies for cancer therapy. Selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-V600E inhibitors Vemurafenib, Encorafenib, and Dabrafenib have been approved by FDA and received remarkable clinical responses, but these drugs are ineffective against RAS mutant tumors due to limited inhibition on dimerized RAF. In this study, we developed a highly potent pan-RAF inhibitor, IHMT-RAF-128, which exhibited similarly high efficacies in inhibiting both partners of the RAF dimer, and showed potent anti-tumor efficacy against a variety of cancer cells harboring either RAF or RAS mutations, especially Adagrasib and Sotorasib (AMG510) resistant-KRAS-G12C secondary mutations, such as KRAS-G12C-Y96C and KRAS-G12C-H95Q. In addition, IHMT-RAF-128 showed excellent pharmacokinetic profile (PK), and the bioavailability in mice and rats were 63.9%, and 144.1%, respectively. Furthermore, IHMT-RAF-128 exhibited potent anti-tumor efficacy on xenograft mouse tumor models in a dose-dependent manner without any obvious toxicities. Together, these results support further investigation of IHMT-RAF-128 as a potential clinical drug candidate for the treatment of cancer patients with RAF or RAS mutations.


Asunto(s)
Neoplasias , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Animales , Ratones , Proteínas Proto-Oncogénicas p21(ras)/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Vemurafenib/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética
5.
Food Res Int ; 169: 112873, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37254321

RESUMEN

The effect of microwave treatment on the content of glucosinolates (GSL) in radish seeds and volatile odor compounds in the microwaved radish seed oils (MRSO) is still unclear. In this study, a total of 13 GSL were identified and quantified in five radish seed varieties by UPLC-IMS-QTOF-MS, among which glucoraphenin, glucoraphasatin, glucoerucin accounting for up to 90 %. Total GSL decreased by 47.39-67.88% after microwave processing. Moreover, 58 odor compounds were identified in MRSO, including 6 sulfides, 12 nitriles, 2 isothiocyanates, 10 alcohols, 12 aldehydes, 5 ketones, 6 acids, and 5 others. The major odor compounds were (methyldisulfanyl)methane, dimethyltrisulfane, (methylsulfinyl)methane, 3-(methylsulfanyl)-1-propanol, methyl thiocyanate, hexanenitrile, 5-(methylsulfanyl)pentanenitrile, and 4-isothiocyanato-1-butene with odor activity value (OAV) higher than 1. The principal components analysis (PCA) results can distinguish MRSO from five different radish seed varieties, three of which (H20-18, H20-19 and H20-28) were in one group and other two (H20-23 and H20-26) were in another group. In addition, aliphatic GSL showed positive correlations with sulfides, isothiocyanates, and nitriles, while negative correlations with alcohols. This work provides a new insight into the odor contribution of GSL degradation products.


Asunto(s)
Raphanus , Glucosinolatos/metabolismo , Odorantes , Microondas , Semillas , Aceites/metabolismo , Isotiocianatos
6.
Plant Physiol Biochem ; 195: 351-361, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36681065

RESUMEN

Radish is an important taproot crop with medicinal and edible uses that is cultivated worldwide. However, the differences in metabolites and the underlying molecular bases among different radish types remain largely unknown. In the present study, a combined analysis of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and RNA-Seq data was conducted to uncover important differentially accumulated metabolites (DAMs) among radish accessions with green, white and red taproot flesh colours. A total of 657 metabolites were identified and 138 DAMs were commonly present in red vs. green and red vs. white accessions. Red accessions were rich in phenolic compounds, while green and white accessions had more amino acids. Additionally, 41 metabolites and 98 genes encoding 37 enzymes were enriched in the shikimate and phenolic biosynthesis pathways. CHS is the rate-limiting enzyme determining flavonoid differences among accessions. A total of 119 candidate genes might contribute to red accession-specific accumulated metabolites. Specifically, one gene cluster consisting of 16 genes, including one RsMYB1, RsMYBL2, RsTT8, RsDFR, RsANS, Rs4CL3, RsSCPL10, Rs3AT1 and RsSAP2 gene, two RsTT19 and RsWRKY44 genes and three RsUGT genes, might be involved in anthocyanin accumulation in red radish fleshy taproots. More importantly, an InDel marker was developed based on an RsMYB1 promoter mutation, and the accuracy reached 95.9% when it was used to select red-fleshed radishes. This study provides comprehensive insights into the metabolite differences and underlying molecular mechanisms in fleshy taproots among different radish genotypes and will be beneficial for the genetic improvement of radish nutritional quality.


Asunto(s)
Raphanus , Raphanus/genética , Raphanus/metabolismo , Transcriptoma , Espectrometría de Masas en Tándem , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Metabolómica , Genotipo
7.
Mol Plant ; 15(11): 1744-1758, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-36176193

RESUMEN

Pepper (Capsicum spp.) is an important vegetable crop that provides a unique pungent sensation when eaten. Through construction of a pepper variome map, we examined the main groups that emerged during domestication and breeding of C. annuum, their relationships and temporal succession, and the molecular events underlying the main transitions. The results showed that the initial differentiation in fruit shape and pungency, increase in fruit weight, and transition from erect to pendent fruits, as well as the recent appearance of large, blocky, sweet fruits (bell peppers), were accompanied by strong selection/fixation of key alleles and introgressions in two large genomic regions. Furthermore, we identified Up, which encodes a BIG GRAIN protein involved in auxin transport, as a key domestication gene that controls erect vs pendent fruit orientation. The up mutation gained increased expression especially in the fruit pedicel through a 579-bp sequence deletion in its 5' upstream region, resulting in the phenotype of pendent fruit. The function of Up was confirmed by virus-induced gene silencing. Taken together, these findings constitute a cornerstone for understanding the domestication and differentiation of a key horticultural crop.


Asunto(s)
Capsicum , Frutas , Frutas/genética , Domesticación , Fitomejoramiento , Capsicum/genética , Fenotipo
9.
Plants (Basel) ; 11(7)2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35406941

RESUMEN

Cucumbers (Cucumis sativus L.) originated from the South Asian subcontinent, and most of them are fragile to cold stress. In this study, we evaluated the cold tolerance of 115 cucumber accessions and screened out 10 accessions showing high resistance to cold stress. We measured and compared plant hormone contents between cold-tolerant cucumber CT90R and cold-sensitive cucumber CT57S in cold treatment. Most of the detected plant hormones showed significantly higher content in CT90R. To elucidate the role of plant hormones, we compared the leaf- and root-transcriptomes of CT90R with those of CT57S in cold stress treatment. In leaves, there were 1209 differentially expressed genes (DEGs) between CT90R and CT57S, while there were 703 in roots. These DEGs were not evenly distributed across the chromosomes and there were significant enrichments at particular positions, including qLTT6.2, a known QTL controlling cucumber cold tolerance. The GO and KEGG enrichment analysis showed that there was a significant difference in the pathway of plant hormone transductions between CT90R and CT57S in leaves. In short, genes involved in plant hormone transductions showed lower transcription levels in CT90R. In roots, the most significantly different pathway was phenylpropanoid biosynthesis. CT90R seemed to actively accumulate more monolignols by upregulating cinnamyl-alcohol dehydrogenase (CAD) genes. These results above suggest a new perspective on the regulation mechanism of cold tolerance in cucumbers.

10.
Acta Pharmacol Sin ; 43(10): 2678-2686, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35228653

RESUMEN

Oncogene HER2 is amplified in 20%-25% of human breast cancers and 6.1%-23.0% of gastric cancers, and HER2-directed therapy significantly improves the outcome for patients with HER2-positive cancers. However, drug resistance is still a clinical challenge due to primary or acquired mutations and drug-induced negative regulatory feedback. In this study, we discovered a potent irreversible HER2 kinase inhibitor, CHMFL-26, which covalently targeted cysteine 805 of HER2 and effectively overcame the drug resistance caused by HER2 V777L, HER2 L755S, HER2 exon 20 insertions, and p95-HER2 truncation mutations. CHMFL-26 displayed potent antiproliferation efficacy against HER2-amplified and mutant cells through constant HER2-mediated signaling pathway inhibition and apoptosis induction. In addition, CHMFL-26 suppressed tumor growth in a dose-dependent manner in xenograft mouse models. Together, these results suggest that CHMFL-26 may be a potential novel anti-HER2 agent for overcoming drug resistance in HER2-positive cancer therapy.


Asunto(s)
Neoplasias de la Mama , Receptor ErbB-2 , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Cisteína , Resistencia a Antineoplásicos , Femenino , Humanos , Ratones , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Int J Mol Sci ; 23(6)2022 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-35328374

RESUMEN

Radish (Raphanus sativus L.) is rich in specific glucosinolates (GSLs), which benefit human health and special flavor formation. Although the basic GSLs metabolic pathway in Brassicaceae plants is clear, the regulating mechanism for specific glucosinolates content in radish fleshy taproots is not well understood. In this study, we discovered that there was a significant difference in the GSLs profiles and the content of various GSLs components. Glucoraphasatin (GRH) is the most predominant GSL in radish taproots of different genotypes as assessed by HPLC analysis. Further, we compared the taproot transcriptomes of three radish genotypes with high and low GSLs content by employing RNA-seq. Totally, we identified forty-one differentially expressed genes related to GSLs metabolism. Among them, thirteen genes (RsBCAT4, RsIPMDH1, RsMAM1a, RsMAM1b, RsCYP79F1, RsGSTF9, RsGGP1, RsSUR1, RsUGT74C1, RsST5b, RsAPK1, RsGSL-OH, and RsMYB28) were significantly higher co-expressed in the high content genotypes than in low content genotype. Notably, correlation analysis indicated that the expression level of RsMYB28, as an R2R3 transcription factor directly regulating aliphatic glucosinolate biosynthesis, was positively correlated with the GRH content. Co-expression network showed that RsMYB28 probably positively regulated the expression of the above genes, particularly RsSUR1, and consequently the synthesis of GRH. Moreover, the molecular mechanism of the accumulation of this 4-carbon (4C) GSL in radish taproots was explored. This study provides new perspectives on the GSLs accumulation mechanism and genetic improvements in radish taproots.


Asunto(s)
Glucosinolatos , Raphanus , Regulación de la Expresión Génica de las Plantas , Humanos , Metaboloma , Raphanus/genética , Raphanus/metabolismo , Transcriptoma
12.
Sheng Wu Gong Cheng Xue Bao ; 38(1): 343-358, 2022 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-35142141

RESUMEN

Three-amino acid loop extension (TALE) transcription factors play important roles in plant growth and cell differentiation. There are plenty of studies on TALE transcription factors in several model plants, but not in radish (Raphanus sativas). A genome-wide bioinformatics analysis identified 33 TALE family genes in the Xiang-Ya-Bai (XYB) radish, These genes, are distributed on nine chromosomes and all contain 4-6 exons. The 33 TALE genes in radish showed a co-linearity relationship with the 17 homologous genes in Arabidopsis thaliana. Moreover, a large number of stress response cis-elements were found in the promoter regions of these genes. Expression analysis showed that four genes in the BELL subfamily were highly expressed in roots, and two genes in the KNOX subfamily were highly expressed in shoots of bolting plants and callus. All radish TALE genes contain sequences encoding the conserved HOX domain, except for the gene RSA10037940, which is homologous to Arabidopsis KNATM. The deduced 3D structures of the TALE proteins irrespective of subtypes are highly similar. All the encoded proteins were weakly acidic and hydrophilic. The radish TALE gene family is relatively evolutionarily conserved, which was consistent with results from Arabidopsis, but quite different from that of rice. This study provides important clues for studying the biological functions of TALE transcription factors in radish.


Asunto(s)
Arabidopsis , Raphanus , Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raphanus/genética , Raphanus/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
13.
Biology (Basel) ; 10(12)2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-34943165

RESUMEN

Raphanus has undergone a lengthy evolutionary process and has rich diversity. However, the inter- and intraspecific phylogenetic relationships and genetic diversity of this genus are not well understood. Through SSR-sequencing and multi-analysis of 939 wild, semi-wild and cultivated accessions, we discovered that the European wild radish (EWR) population is separated from cultivated radishes and has a higher genetic diversity. Frequent intraspecific genetic exchanges occurred in the whole cultivated radish (WCR) population; there was considerable genetic differentiation within the European cultivated radish (ECR) population, which could drive radish diversity formation. Among the ECR subpopulations, European primitive cultivated radishes (EPCRs) with higher genetic diversity are most closely related to the EWR population and exhibit a gene flow with rat-tail radishes (RTRs) and black radishes (BRs)/oil radishes (ORs). Among Asian cultivated radishes (ACRs), Chinese big radishes (CBRs) with a relatively high diversity are furthest from the EWR population, and most Japanese/Korean big radishes (JKBRs) are close to CBR accessions, except for a few old Japanese landraces that are closer to the EPCR. The CBR and JKBR accessions are independent of RTR accessions; however, phylogenetic analysis indicates that the RTR is sister to the clade of CBR (including JWR), which suggests that the RTR may share the most recent common ancestry with CBRs and JWRs. In addition, Japanese wild radishes (JWRs), (namely, R. sativus forma raphanistroides) are mainly scattered between CBRs and EPCRs in PCoA analysis. Moreover, JWRs have a strong gene exchange with the JKBR, OR and RTR subpopulations. American wild radishes (AWRs) are closely related to European wild and cultivated radishes, and have a gene flow with European small radishes (ESRs), suggesting that the AWR developed from natural hybridization between the EWR and the ESR. Overall, this demonstrates that Europe was the origin center of the radish, and that Europe, South Asia and East Asia appear to have been three independent domestication centers. The EPCR, AWR and JWR, as semi-wild populations, might have played indispensable transitional roles in radish evolution. Our study provides new perspectives into the origin, evolution and genetic diversity of Raphanus and facilitates the conservation and exploitation of radish germplasm resources.

14.
Mol Plant ; 14(12): 2032-2055, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-34384905

RESUMEN

Post-polyploid diploidization associated with descending dysploidy and interspecific introgression drives plant genome evolution by unclear mechanisms. Raphanus is an economically and ecologically important Brassiceae genus and model system for studying post-polyploidization genome evolution and introgression. Here, we report the de novo sequence assemblies for 11 genomes covering most of the typical sub-species and varieties of domesticated, wild and weedy radishes from East Asia, South Asia, Europe, and America. Divergence among the species, sub-species, and South/East Asian types coincided with Quaternary glaciations. A genus-level pan-genome was constructed with family-based, locus-based, and graph-based methods, and whole-genome comparisons revealed genetic variations ranging from single-nucleotide polymorphisms (SNPs) to inversions and translocations of whole ancestral karyotype (AK) blocks. Extensive gene flow occurred between wild, weedy, and domesticated radishes. High frequencies of genome reshuffling, biased retention, and large-fragment translocation have shaped the genomic diversity. Most variety-specific gene-rich blocks showed large structural variations. Extensive translocation and tandem duplication of dispensable genes were revealed in two large rearrangement-rich islands. Disease resistance genes mostly resided on specific and dispensable loci. Variations causing the loss of function of enzymes modulating gibberellin deactivation were identified and could play an important role in phenotype divergence and adaptive evolution. This study provides new insights into the genomic evolution underlying post-polyploid diploidization and lays the foundation for genetic improvement of radish crops, biological control of weeds, and protection of wild species' germplasms.


Asunto(s)
Domesticación , Flujo Génico , Variación Genética , Fenotipo , Raphanus/genética , Productos Agrícolas , Evolución Molecular , Genes de Plantas , Filogenia , Malezas , Poliploidía
15.
Eur J Pharmacol ; 897: 173944, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33581133

RESUMEN

As the critical driving force for chronic myeloid leukemia (CML), BCR gene fused ABL kinase has been extensively explored as a validated target of drug discovery. Although imatinib has achieved tremendous success as the first-line treatment for CML, the long-term application ultimately leads to resistance, primarily via various acquired mutations occurring in the BCR-ABL kinase. Although dasatinib and nilotinib have been approved as second-line therapies that could overcome some of these mutants, the most prevalent gatekeeper T315I mutant remains unconquered. Here, we report a novel type II kinase inhibitor, CHMFL-48, that potently inhibits the wild-type BCR-ABL (wt) kinase as well as a panel of imatinib-resistant mutants, including T315I, F317L, E255K, Y253F, and M351T. CHMFL-48 displayed great inhibitory activity against ABL wt (IC50: 1 nM, 70-fold better than imatinib) and the ABL T315I mutant (IC50: 0.8 nM, over 10,000-fold better than imatinib) in a biochemical assay and potently blocked the autophosphorylation of BCR-ABL wt and BCR-ABL mutants in a cellular context, which further affected downstream signalling mediators, including signal transducer and activator of transcription 5 (STAT5) and CRK like proto-oncogene (CRKL), and led to the cell cycle progression blockage as well as apoptosis induction. CHMFL-48 also exhibited great anti-leukemic efficacies in vivo in K562 cells and p210-T315I-transformed BaF3 cell-inoculated murine models. This discovery extended the pharmacological diversity of BCR-ABL kinase inhibitors and provided more potential options for anti-CML therapies.


Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Mesilato de Imatinib/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/metabolismo , Fusión Génica , Humanos , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Ratones , Ratones Desnudos , Mutación , Proto-Oncogenes Mas , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Chembiochem ; 22(1): 129-133, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-32979005

RESUMEN

Ibrutinib is an FDA-approved drug to treat B-lymphoid malignancies, which functions mechanistically as a covalent inhibitor for Bruton's tyrosine kinase (BTK). During the course of screening more potent and selective BTK inhibitors, we discovered that MM2-48, an ibrutinib analogue that contains the alkynyl amide functional group in place of the acrylamide warhead, exhibits a much stronger cytotoxicity. Comparative chemoproteomic profiling of the targets of ibrutinib and MM2-48 revealed that the alkynyl amide warhead exhibits much higher reactivity in proteomes. Unexpectedly, MM2-48 covalently targets a functional cysteine in a BRCA2 and CDKN1A-interacting protein, BCCIP, and significantly inhibits DNA damage repair. Our findings suggest that simultaneous inhibition of BTK activity and DNA damage repair might be a more effective therapeutic strategy for combating B-cell malignancies.


Asunto(s)
Adenina/análogos & derivados , Proteína BRCA2/antagonistas & inhibidores , Proteínas de Unión al Calcio/antagonistas & inhibidores , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas Nucleares/antagonistas & inhibidores , Piperidinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteómica , Adenina/química , Adenina/farmacología , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Agammaglobulinemia Tirosina Quinasa/metabolismo , Proteína BRCA2/química , Proteína BRCA2/metabolismo , Proteínas de Unión al Calcio/química , Proteínas de Unión al Calcio/metabolismo , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Daño del ADN , Humanos , Estructura Molecular , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Piperidinas/química , Inhibidores de Proteínas Quinasas/química
17.
Plant Physiol Biochem ; 158: 34-42, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33296844

RESUMEN

Garlic (Allium sativum L.) is an economically important vegetable crop which is used worldwide for culinary and medicinal purposes. Soil salinity constrains the yield components of garlic. Understanding the responsive mechanism of garlic to salinity is crucial to improve its tolerance. To address this problem, two garlic cultivars differing in salt tolerance were used to investigate the long-term adaptive responses to salt stress at phenotype and transcriptome levels. Phenotypic analysis showed four-week salt stress significantly decreased the yield components of salt-sensitive cultivar. Transcriptomes of garlics were de novo assembled and mined for transcriptional activities regulated by salt stress. The results showed that photosynthesis, energy allocation, and secondary metabolism were commonly enriched in both sensitive and tolerant genotypes. Moreover, distinct responsive patterns were also observed between the two genotypes. Compared with the salt-tolerant genotype, most transcripts encoding enzymes in the phenylpropanoid biosynthesis pathway were coordinately down regulated in the salt-sensitive genotype, resulting in alternation of the content and composition of lignin. Meanwhile, transcripts encoding the enzymes in the brassinosteroid (BR) biosynthesis pathway were also systematically down regulated in the salt-sensitive genotypes. Taken together, these results suggested that BR-mediated lignin accumulation possibly plays an important role in garlic adaption to salt stress. These findings expand the understanding of responsive mechanism of garlic to salt stress.


Asunto(s)
Brasinoesteroides/química , Ajo/fisiología , Lignina/química , Estrés Salino , Estrés Fisiológico , Transcriptoma , Ajo/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genotipo
18.
Sci Rep ; 10(1): 4867, 2020 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-32184427

RESUMEN

High callus production is a feasible way to improve the propagation coefficient of garlic. It remains unknown how genotypes and explants affect garlic callus formation. In the present investigation, we found that there were significant differences in callus formation among garlic varieties. Tip explants were the best calli-producing source, and 91.05% of the explants from four varieties, on average, formed calli after 45 d of primary culturing. Upper leaf parts explants produced lower values. Among the different varieties and explant types, tip explants of variety T141 induced calli in the shortest time and had the greatest callus fresh weight at 45 d. An endogenous hormone contents analysis showed that auxins (indole-3-acetic acid and methyl indole-3-acetic acetate), cytokinins (trans-zeatin and dihydrozeatin), gibberellins4, 9,15,19,24 and 53, abscisic acid, jasmonic acid, jasmonoyl-L-isoleucine, and dihydrojasmonic acid were significantly greater in the tips than those in the upper leaf parts. High endogenous jasmonic acid content might play important roles in callus formation. These results will help us not only establish an efficient garlic callus induction protocol that can be applied to large-scale callus multiplication and regeneration, and to genetically improvement of garlic production, but also understand endogenous hormone roles in tissue/organ differentiation and dedifferentiation.


Asunto(s)
Ajo/crecimiento & desarrollo , Ajo/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Ácido Abscísico/metabolismo , Citocininas/metabolismo , Ajo/metabolismo , Genotipo , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Especificidad de Órganos , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Cultivo Primario de Células/métodos
19.
Front Genet ; 10: 808, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31608100

RESUMEN

Taproot skin color is a crucial visual and nutritional quality trait of radish, and purple skin is most attractive to consumers. However, the genetic mechanism underlying this character is unknown. Herein, F2 segregating populations were constructed to investigate radish genomic regions with purple skin genes. Segregation analysis suggested that pigment presence was controlled by one dominant gene, Rsps. A bulk segregant approach coupled to whole-genome sequencing (QTL-seq) and classical linkage mapping narrowed the Rsps location to a 238.51-kb region containing 18 genes. A gene in this region, designated RsMYB1.1 (an Arabidopsis PAP1 homolog), was a likely candidate gene because semiquantitative RT-PCR and quantitative real-time PCR revealed RsMYB1.1 expression in only purple-skinned genotypes, sequence variation was found between white- and purple-skinned radishes, and an InDel marker in this gene correctly predicted taproot skin color. Furthermore, four RsMYB1.1 homologs (RsMYB1.1-1.4) were found in "XYB36-2" radish. RsMYB1.1 and the previously mapped and cloned RsMYB1.4 (contributing to red skin) were located on different chromosomes and in different subclades of a phylogenetic tree; thus, they are different genes. These findings provide insight into the complex anthocyanin biosynthesis regulation in radish and information for molecular breeding to improve the anthocyanin content and appearance of radish taproots.

20.
BMC Genomics ; 20(1): 371, 2019 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-31088355

RESUMEN

BACKGROUND: Barbarea vulgaris is a wild cruciferous plant and include two distinct types: the G- and P-types named after their glabrous and pubescent leaves, respectively. The types differ significantly in resistance to a range of insects and diseases as well as glucosinolates and other chemical defenses. A high-density linkage map was needed for further progress to be made in the molecular research of this plant. RESULTS: We performed restriction site-associated DNA sequencing (RAD-Seq) on an F2 population generated from G- and P-type B. vulgaris. A total of 1545 SNP markers were mapped and ordered in eight linkage groups, which represents the highest density linkage map to date for the crucifer tribe Cardamineae. A total of 722 previously published genome contigs (50.2 Mb, 30% of the total length) can be anchored to this high density genetic map, an improvement compared to a previously published map (431 anchored contigs, 38.7 Mb, 23% of the assembly genome). Most of these (572 contigs, 31.2 Mb) were newly anchored to the map, representing a significant improvement. On the basis of the present high-density genetic map, 37 QTL were detected for eleven traits, each QTL explaining 2.9-71.3% of the phenotype variation. QTL of glucosinolates, leaf size and color traits were in most cases overlapping, possibly implying a functional connection. CONCLUSIONS: This high-density linkage map and the QTL obtained in this study will be useful for further understanding of the genetic of the B. vulgaris and molecular basis of these traits, many of which are shared in the related crop watercress.


Asunto(s)
Barbarea/genética , Mapeo Cromosómico/métodos , Sitios de Carácter Cuantitativo , Análisis de Secuencia de ADN/métodos , Barbarea/fisiología , ADN de Plantas/genética , Ligamiento Genético , Fenotipo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Polimorfismo de Nucleótido Simple
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