更新于：2024-09-19

PATJ

更新于：2024-09-19

基本信息

别名

Channel-interacting PDZ domain-containing protein、Cipp、hINADL

+ [7]

简介

Scaffolding protein that facilitates the localization of proteins to the cell membrane (PubMed:11927608, PubMed:16678097, PubMed:22006950). Required for the correct formation of tight junctions and epithelial apico-basal polarity (PubMed:11927608, PubMed:16678097). Positively regulates epithelial cell microtubule elongation and cell migration, possibly via facilitating localization of PRKCI/aPKC and PAR3D/PAR3 at the leading edge of migrating cells (By similarity). Plays a role in the correct reorientation of the microtubule-organizing center during epithelial migration (By similarity). May regulate the surface expression and/or function of ASIC3 in sensory neurons (By similarity). May recruit ARHGEF18 to apical cell-cell boundaries (PubMed:22006950).

关联

100 项与 PATJ 相关的临床结果

登录后查看更多信息

100 项与 PATJ 相关的转化医学

登录后查看更多信息

0 项与 PATJ 相关的专利（医药）

登录后查看更多信息

150

项与 PATJ 相关的文献（医药）

2024-08-15·Nature

Membrane prewetting by condensates promotes tight-junction belt formation

Article

作者: Martin-Lemaitre, Cecilie ; Adame-Arana, Omar ; Jülicher, Frank ; Honigmann, Alf ; Pombo-García, Karina

AbstractBiomolecular condensates enable cell compartmentalization by acting as membraneless organelles1. How cells control the interactions of condensates with other cellular structures such as membranes to drive morphological transitions remains poorly understood. We discovered that formation of a tight-junction belt, which is essential for sealing epithelial tissues, is driven by a wetting phenomenon that promotes the growth of a condensed ZO-1 layer2 around the apical membrane interface. Using temporal proximity proteomics in combination with imaging and thermodynamic theory, we found that the polarity protein PATJ mediates a transition of ZO-1 into a condensed surface layer that elongates around the apical interface. In line with the experimental observations, our theory of condensate growth shows that the speed of elongation depends on the binding affinity of ZO-1 to the apical interface and is constant. Here, using PATJ mutations, we show that ZO-1 interface binding is necessary and sufficient for tight-junction belt formation. Our results demonstrate how cells exploit the collective biophysical properties of protein condensates at membrane interfaces to shape mesoscale structures.

2024-05-01·Asian Pacific Journal of Cancer Prevention

Identification of Potential Breast Cancer Stem Cell Biomarkers in the Secretome Using a Network Interaction Approach Analysis

Article

作者: Margaret, Ay Ly ; Wanandi, Septelias Inawati ; Paramita, Rafika Indah ; Fadilah, Fadilah

BACKGROUNDBreast cancer stem cells (BCSCs) play a role in the high rates of resistance, recurrence, and metastasis. The precise biomarkers of BCSCs can assist effectively in identifying cancer, assessing prognosis, diagnosing, and monitoring therapy. The aim of this study was to give a complete analysis for predicting specific biomarkers of BCSCs.METHODSWe aggregated profile datasets in this work to shed light on the underlying critical genes and pathways of BCSCs. We obtained two expression profiling by array datasets (GSE7513 and GSE7515) from the Gene Expression Omnibus (GEO) database to identify biomarkers in BCSCs. Enrichr was used to do functional analysis, including gene ontology (GO) and reactome pathway. Furthermore, the protein-protein interaction (PPI) of these differential expression genes (DEGs) was visualized using Cytoscape with the search tool for the retrieval of interacting genes (STRING). The hub genes in the PPI network were chosen for further investigation.RESULTSWe identified 65 up-regulated and 190 down- regulated DEGs and the GO enrichment analysis revealed that these DEGs were enriched in biological process related to tumorigenesis and stemness, including alter the extracellular matrix's physicochemical properties, cytoskeletal reorganisation, adhesion, motility, migration, growth, and survival. The Reactome analysis indicated that these DEGs were also involved in modulating function of ECM, regulation cancer metabolism and angiogenesis, tumor growth, proliferation, and metastasis.CONCLUSIONOur bioinformatic study revealed that FYN, INADL, OCLN, F11R, and TOP2A were potential biomarker panel of BCSCs from secretome.

2024-04-15·Leukemia & Lymphoma

The CIpP activator, TR-57, is highly effective as a single agent and in combination with venetoclax against CLL cells in vitro

Article

作者: Mulligan, Stephen P ; Iwanowicz, Edwin J ; Lang, Henk ; Burling, Olivia ; Thurgood, Lauren ; Crassini, Kyle ; Fatima, Narjis ; Karanewsky, Donald S ; Shen, Yandong ; Best, O Giles ; Christopherson, Richard I

Despite advances in treatment, a significant proportion of patients with chronic lymphocytic leukemia (CLL) will relapse with drug-resistant disease. The imipridones, ONC-201 and ONC-212, are effective against a range of different cancers, including acute myeloid leukemia (AML) and tumors of the brain, breast, and prostate. These drugs induce cell death through activation of the mitochondrial protease, caseinolytic protease (CIpP), and the unfolded protein response (UPR). Here we demonstrate that the novel imipridone analog, TR-57, has efficacy as a single agent and synergises with venetoclax against CLL cells under in vitro conditions that mimic the tumor microenvironment. Changes in protein expression suggest TR-57 activates the UPR, inhibits the AKT and ERK1/2 pathways and induces pro-apoptotic changes in the expression of proteins of the BCL-2 family. The study suggests that TR-57, as a single agent and in combination with venetoclax, may represent an effective treatment option for CLL.

项与 PATJ 相关的新闻（医药）

2023-07-14

·生物谷

Nature子刊：午睡受基因调控，适度午睡降低痴呆风险，有助心脏健康

午睡是一种受到基因控制的生物节律，它不仅与人的精神状态有关，还与人的健康密切相关。适当的午睡不仅可以提高认知能力和降低痴呆症的患病风险，还能改善心脏代谢健康；但过度午睡反而会导致高血压和腰围增加。在现代社会，随着工作和生活节奏的加快，以及各种娱乐活动的干扰，很少人能拥有充足的睡眠时间。然而，睡眠对人的健康十分关键，从某种意义上来说，睡眠质量在很大程度上决定着生活质量。值得注意的是，午睡作为自然睡眠周期的重要组成部分，却被越来越多的人舍弃、忽视甚至遗忘。实际上，午睡不仅可以弥补夜间失眠造成的影响，还能消除工作带来的紧张和烦躁感，使人保持良好的精神状态。 2021年2月，美国麻省总医院（MGH）的研究人员在 Nature 子刊 Nature Communications 上发表了题为：Genetic determinants of daytime napping and effects on cardiometabolic health 的研究论文【1】。这项研究发现了人类基因组中123个与白天午睡有关的区域，以及三种促进午睡的不同机制。该研究还表明午睡习惯与心脏代谢健康有关，不仅如此，许多与午睡有关的基因也与人体健康密切相关。午睡是效率最高的睡眠，同时也是一种对人体保持清醒必不可少的生物节律。有研究表明，有规律的午睡与更好的认知功能以及更低的痴呆症发病风险相关；然而，另一些研究却表明，白天过度嗜睡反而会增加痴呆症或认知衰退的风险。 2021年1月25日，上海交通大学孙林教授和安徽芜湖市第四人民医院韩彩教授等人在 General Psychiatry期刊发表了题为：Relationship between afternoon napping and cognitive function in the ageing Chinese population 的研究论文【2】。该研究表明，午睡能有效预防老年痴呆，并且有规律的午睡还可以提高思维敏捷性。实际上，在人类社会中，午睡是否必要一直是一个争议性问题。一些长期以来拥有“午睡文化”的国家，如西班牙，如今都不再鼓励这一习惯。但与此同时，美国的一些公司却提倡用午间打盹来提升员工的午后精神状态。因此，揭开导致我们午睡的生物学通路是十分重要的。在这项研究中，麻省总医院的研究人员使用了来自英国生物样本库（UK Biobank）的数据，共包含了452633人的基因信息。所有参与者都被问及午睡的频率——包括“从不/很少午睡”、“有时午睡”以及“经常午睡”。其中，一小部分参与者佩戴了活动监测器，以此确定这些参与者是否午睡。根据这些数据，研究小组再通过全基因组关联分析（GWAS）在人类基因组中确定了123个与午睡相关的基因区域。研究结果包括：治疗睡眠障碍的药物靶点（HCRTR1、HCRTR2）的错义变异，与觉醒相关的基因（TRPC6、PNOC），以及肥胖-嗜睡通路的基因（PNOC、PATJ）。与午睡相关的基因区域不仅如此，该研究的其他介个特征也支持了这一结果，例如，研究人员对基因检测公司23andMe收集的541333人的基因组分析中独立重复了他们的发现。此外，在全基因组关联分析（GWAS）识别的区域附近或区域的大量基因已经被发现在睡眠中发挥作用，比如KSR2。 UK Biobank和23andMe数据的全基因组关联分析结果是一致的深入分析研究数据后，研究小组发现了至少三种促进午睡的潜在机制：睡眠倾向：有些人比其他人需要更多的睡眠；睡眠中断：午睡可以帮助弥补睡眠质量差或夜间失眠的影响；起的太早：早起的人可能会再午间打个盹补觉。这些试验结果表明，午睡是一种由基因驱动的行为，而不仅仅是环境或行为选择。更重要的是，研究人员还通过聚类分析确定了三种促进午睡的不同机制，这些机制还与心脏代谢结果的异质性相关。孟德尔随机分组法表明，白天更频繁的午睡与高血压和腰围增加之间存在潜在的因果关系。数据分析表明午睡基因与心脏代谢健康等指标相关除此之外，一些与午睡有关的基因变异还被证实与一种叫食欲素（orexin）的神经肽存在联系，这种神经肽在清醒状态中起着重要作用。此前的研究表明，食欲素与嗜睡症等罕见的睡眠障碍有关。全基因组基因结构与日间午睡的相关性及与疾病和性状的相关性由此看来，午睡是一种受到基因控制的生物节律，它不仅与人的精神状态有关，还与人的健康密切相关。适当的午睡不仅可以提高认知能力和降低痴呆症的患病风险，还能改善心脏代谢健康；但过度午睡反而会导致高血压和腰围增加。