更新于：2024-11-01

YWHAZ

更新于：2024-11-01

基本信息

别名

14-3-3 protein zeta/delta、14-3-3-zeta、KCIP-1

+ [4]

简介

Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity).

关联

项与 YWHAZ 相关的药物

CN115838436

专利挖掘

靶点

YWHAZ

作用机制-

在研机构

中国医科大学附属第一医院

原研机构

中国医科大学附属第一医院

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 YWHAZ 相关的临床结果

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100 项与 YWHAZ 相关的转化医学

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0 项与 YWHAZ 相关的专利（医药）

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619

项与 YWHAZ 相关的文献（医药）

2024-12-01·Molecular Biology Reports

Comprehensive evaluation and validation of optimal reference genes for normalization of qPCR data in different caprine tissues

Article

作者: Vasu, Mahanthi ; Arora, Reena ; Sharma, Rekha ; Mir, M A ; Singh, Manoj Kumar ; Choudhary, Vikas ; Ahlawat, Sonika

BACKGROUNDQuantitative real-time PCR (qPCR) is a highly reliable method for validating gene expression data in molecular studies due to its sensitivity, specificity, and efficiency. To ensure accurate qPCR results, it's essential to normalize the expression data using stable reference genes.METHODSThis study aimed to identify suitable reference genes for qPCR studies in goats by evaluating 18 candidate reference genes (ACTB, BACH1, B2M, GAPDH, HMBS, HPRT1, PGK1, PPIA, PPIB, RPLP0, RPL19, RPS9, RPS15, RPS28, SDHA, TBP, UXT, and YWHAZ) in 10 different caprine tissues (heart, intestine, kidney, liver, lung, muscle, rumen, skin, spleen, and testis). An integrated tool called RefFinder, which incorporates various algorithms like NormFinder, GeNorm, BestKeeper, and ΔCt, was used to assess the stability of expression among these genes.RESULTSAfter thorough analysis, ACTB, PPIB, and B2M emerged as the most stable reference genes, while RPL19, RPS15, and RPS9 were found to be the least stable. The suitability of the selected internal control genes was further validated through target gene analysis, confirming their efficacy in ensuring accurate gene expression profiling in goats.CONCLUSIONThe study determined that the geometric average of ACTB, PPIB, and B2M creates an appropriate normalization factor for gene expression studies in goat tissues.

2024-12-01·International Immunopharmacology

Bioinformatics data combined with single-cell analysis reveals patterns of immunoinflammatory infiltration and cell death in melanoma

Article

作者: Cui, Fan ; Liu, Yangying ; Rang, Zhen ; Yang, Ge ; Jin, Li

BACKGRUONDMelanoma is a common cancer in dermatology, but its molecular mechanisms remain poorly explained.AIMUtilizing single-cell analytics and bioinformatics, the work sought to discover the immunological infiltration and cellular molecular mechanisms of melanoma.METHODSMelanoma genes databases were downloaded from GeneCards, and gene expression profiles were chosen from the Gene Expression Omnibus (GSE244889). Establishing and analyzing protein-protein interaction networks for functional enrichment made use of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. The process assesses the immunological cell infiltration variations between normal and malignant samples by Immune Cell AI software program. Different cell type differences were clarified by cell quality control, filtration, removal of batch effects and cell clustering analysis using single cell analysis techniques.RESULTSUsing a variety of machine learning techniques, 20 differentially expressed hub genes were found; among these, TP53, HSP90AB1, HSPA4, RHOA, CCND1, CYCS, PPARG, NFKBIA, CAV1, ANXA5, ENO1, ITGAM, YWHAZ, RELA, SOD1, and VDAC1 were found to be significantly significant. The results of enrichment analysis demonstrated that immune response and inflammatory response were strongly associated with melanoma. Animal mitophagy, ferroptosis, the PI3K-Akt signaling pathway, and the HIF-1 signaling pathway were the primary signaling pathways implicated. Cells of immunity, T-cells, lymphocytes, B-cells, NK-cells, monocytes, and macrophages were shown to be significantly infiltrated in melanoma patients, according to analysis. Single cell analysis also demonstrated that ferroptosis is a significant mechanism of cell death that contributes to the advancement of melanoma and that macrophages are important in the disease.CONCLUSIONIn summary, different immune cell infiltrations-particularly macrophages-have a significant impact on the onset and course of melanoma, and our findings may help direct future investigations into melanoma macrophages.

2024-09-16·Proteomics

Matrix stiffness regulates the protein profile of extracellular vesicles of pancreatic cancer cell lines.

Article

作者: Simanic, Isidora ; Cohen, José ; Gazeau, Florence ; Bourgoin-Voillard, Sandrine ; Cascone, Ilaria ; Habert, Damien ; Courty, José ; Vallée, Benoit ; Ferrara, Benedetta ; Nicolas-Boluda, Alba ; Vingert, Benoit ; Seve, Michel ; Castellano, Flavia

The fibrotic stroma characterizing pancreatic ductal adenocarcinoma (PDAC) derives from a progressive tissue rigidification, which induces epithelial mesenchymal transition and metastatic dissemination. The aim of this study was to investigate the influence of matrix stiffness on PDAC progression by analyzing the proteome of PDAC-derived extracellular vesicles (EVs). PDAC cell lines (mPDAC and KPC) were grown on synthetic supports with a stiffness close to non-tumor (NT) or tumor tissue (T), and the protein expression levels in cell-derived EVs were analyzed by a quantitative MS^E label-free mass spectrometry approach. Our analysis figured out 15 differentially expressed proteins (DEPs) in mPDAC-EVs and 20 DEPs in KPC-EVs in response to matrix rigidification. Up-regulated proteins participate to the processes of metabolism, matrix remodeling, and immune response, altogether hallmarks of PDAC progression. A multimodal network analysis revealed that the majority of DEPs are strongly related to pancreatic cancer. Interestingly, among DEPs, 11 related genes (ACTB/ANXA7/C3/IGSF8/LAMC1/LGALS3/PCD6IP/SFN/TPM3/VARS/YWHAZ) for mPDAC-EVs and 9 (ACTB/ALDH2/GAPDH/HNRNPA2B/ITGA2/NEXN/PKM/RPN1/S100A6) for KPC-EVs were significantly overexpressed in tumor tissues according to gene expression profiling interaction analysis (GEPIA). Concerning the potential clinical relevance of these data, the cluster of ACTB, ITGA2, GAPDH and PKM genes displayed an adverse effect (p < 0.05) on the overall survival of PDAC patients.

项与 YWHAZ 相关的新闻（医药）

2023-08-22

·生物谷

北京大学肿瘤医院与研究所研究者们揭示了YWHAZ是胰腺癌转移的关键调节因子

胰腺导管腺癌是胰腺癌中最常见的一种。它是美国癌症死亡的第四大原因。其高病死率可能是由于大多数局部晚期肿瘤和/或转移的PDAC患者诊断较晚所致。胰腺导管腺癌是胰腺癌中最常见的一种。它是美国癌症死亡的第四大原因。其高病死率可能是由于大多数局部晚期肿瘤和/或转移的PDAC患者诊断较晚所致。因此，需要对胰腺癌转移的分子发病机制进行深入研究，以期探索新的有效的治疗策略和临床治疗方法。图片来源：https://doi.org/10.1038/s41419-023-05951-5 近日，来自北京大学肿瘤医院与研究所的研究者们在Cell Death and Disease杂志上发表了题为“High-throughput functional screen identifies YWHAZ as a key regulator of pancreatic cancer metastasis”的文章，该研究通过高通量功能筛查确定YWHAZ是胰腺癌转移的关键调节因子。胰腺癌是癌症死亡的主要原因，因为它的早期转移和对现有治疗方法的反应有限。转移是一个复杂的多步骤过程，是由复杂的基因改变决定的。尽管已经确定了许多与转移相关的基因，但将司机与众多乘客区分开来，并在癌症病理生理学中确定因果关系仍然具有挑战性。在本研究中，研究者建立了一个高通量和基于猪Bac转座子的遗传筛选平台，该平台能够使染色体基因在包含多西环素调控启动子的基因搜索载体盒的掺入部位附近表达减少或增加。利用这一策略，研究者确定YWHAZ是胰腺癌转移的关键调节因子。研究者证明了基因搜索载体对Ywhaz基因的功能性激活导致了小鼠胰腺癌细胞转移能力的增强。YWHAZ的转移促进作用在人胰腺癌细胞中得到进一步验证。过表达YWHAZ通过调节上皮细胞向间充质细胞的转变，在体外导致更具侵袭性的转移表型和更短的体内存活率。因此，本研究建立了一种高通量筛选方法来研究新基因的功能相关性，并证实YWHAZ是胰腺癌转移的关键调节因子。 YWHAZ通过EMT促进胰腺癌转移图片来源：https://doi.org/10.1038/s41419-023-05951-5 综上所述，本研究建立了一种基于piggyBac转座子的可调控插入突变系统，用于体内功能筛选小鼠胰腺癌转移相关基因。本研究共鉴定了16个基因和一个与转移表型直接相关的长非编码RNA。据报道，它们中的一些参与了转移，但其他的没有。YWHAZ在胰腺癌转移中的作用在体外和体内都得到了功能验证。这些发现表明，调控功能基因组筛选是识别肿瘤转移相关基因的有效工具。这些已识别的基因可能会为癌症转移的潜在机制提供新的见解，并为治疗胰腺癌提供新的治疗策略。（生物谷 Bioon.com）参考文献 Fang Cao et al. High-throughput functional screen identifies YWHAZ as a key regulator of pancreatic cancer metastasis. Cell Death Dis. 2023 Jul 14;14(7):431. doi: 10.1038/s41419-023-05951-5.