更新于：2024-11-01

LBR

更新于：2024-11-01

基本信息

别名

3-beta-hydroxysterol Delta (14)-reductase、C-14 sterol reductase、C14SR

+ [10]

简介

Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis (PubMed:9630650, PubMed:12618959, PubMed:16784888, PubMed:21327084, PubMed:27336722). Plays a critical role in myeloid cell cholesterol biosynthesis which is essential to both myeloid cell growth and functional maturation (By similarity). Mediates the activation of NADPH oxidases, perhaps by maintaining critical levels of cholesterol required for membrane lipid raft formation during neutrophil differentiation (By similarity). Anchors the lamina and the heterochromatin to the inner nuclear membrane (PubMed:10828963).

关联

项与 LBR 相关的药物

CN113652428

专利挖掘

靶点

LBR

作用机制-

在研机构

南通工学院

原研机构

南通工学院

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 LBR 相关的临床结果

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100 项与 LBR 相关的转化医学

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0 项与 LBR 相关的专利（医药）

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527

项与 LBR 相关的文献（医药）

2024-12-01·Molecular Biology Reports

Interaction with B-type lamin reveals the function of Drosophila Keap1 xenobiotic response factor in nuclear architecture

Article

作者: Cross, Bethany ; Cook, Isabel ; Neidviecky, Emma ; Carlson, Jennifer ; Deng, Huai

BACKGROUNDThe Keap1-Nrf2 pathway serves as a central regulator that mediates transcriptional responses to xenobiotic and oxidative stimuli. Recent studies have shown that Keap1 and Nrf2 can regulate transcripts beyond antioxidant and detoxifying genes, yet the underlying mechanisms remain unclear. Our research has uncovered that Drosophila Keap1 (dKeap1) and Nrf2 (CncC) proteins can control high-order chromatin structure, including heterochromatin.METHODS AND RESULTSIn this study, we identified the molecular interaction between dKeap1 and lamin Dm0, the Drosophila B-type lamin responsible for the architecture of nuclear lamina and chromatin. Ectopic expression of dKeap1 led to an ectopic localization of lamin to the intra-nuclear area, corelated with the spreading of the heterochromatin marker H3K9me2 into euchromatin regions. Additionally, mis-regulated dKeap1 disrupted the morphology of the nuclear lamina. Knocking down of dKeap1 partially rescued the lethality induced by lamin overexpression, suggesting their genetic interaction during development.CONCLUSIONSThe discovered dKeap1-lamin interaction suggests a novel role for the Keap1 oxidative/xenobiotic response factor in regulating chromatin architecture.

2024-10-01·Molecular and Cellular Endocrinology

Dual inhibition of AKT and ERK1/2 pathways restores the expression of progesterone Receptor-B in endometriotic lesions through epigenetic mechanisms

Article

作者: Arosh, Joe A ; Banu, Sakhila K ; Lee, JeHoon ; Dutta, Sudipta

Endometriosis is an estrogen-dependent and progesterone-resistant gynecological inflammatory disease of reproductive-age women. Progesterone resistance, loss of progesterone receptor -B (PR-B) in the stromal cells of the endometrium, is one of the hallmarks of endometriosis and a major contributing factor for infertility in endometriosis patients. Loss of PR-B in the stromal cells of the endometriotic lesions poses resistance to the success of progesterone-based therapy. The working hypothesis is that PR-B is hypermethylated and epigenetically silenced, and inhibition of AKT and ERK1/2 pathways will decrease the hypermethylation, reverse the epigenetic silencing, and restore the expression of PR-B via DNA methylation and histone modification mechanisms in the endometriotic lesions. The objectives are to (i) determine the effects of dual inhibition of AKT and ERK1/2 pathways on the expression of PR-B and DNA methylation and histone modification protein machinery in the endometriotic lesions and (ii) identify the underlying epigenetic mechanisms of PR-B restoration in the endometriotic lesions. The results indicate that dual inhibition of AKT and ERK1/2 pathways decreases the hypermethylation, reverses the epigenetic silencing, and restores the expression of PR-B via DNA methylation and H3K9 and H3K27 methylation mechanisms in the endometriotic lesions or endometriotic stromal cells of human origin. These results support the novel concept that restored expression of PR-B in the endometriotic lesions and endometrium may improve the clinical outcome of progesterone therapy in endometriosis patients.

2024-10-01·Cell Reports

Mitotic ER-mitochondria contact enhances mitochondrial Ca2+ influx to promote cell division

Article

作者: Jia, Mingkang ; Xin, Guangwei ; Wang, Xiangyang ; Jiang, Qing ; Sun, Mengjie ; Zhu, Shicong ; Lin, Qiaoyu ; Zhao, Gan ; Zhang, Chuanmao ; Ren, He ; Wang, Guopeng

Cell division is tightly regulated and requires an expanded energy supply. However, how this energy is generated remains unclear. Here, we establish a correlation between two mitochondrial Ca²⁺ influx events and ATP production during mitosis. While both events promote ATP production during mitosis, the second event, the Ca²⁺ influx surge, is substantial. To facilitate this Ca²⁺ influx surge, the lamin B receptor (LBR) organizes a mitosis-specific endoplasmic reticulum (ER)-mitochondrial contact site (ERMCS), creating a rapid Ca²⁺ transport pathway. LBR acts as a tether, connecting the ER Ca²⁺ release channel IP₃R with the mitochondrial VDAC2. Depletion of LBR disrupts the Ca²⁺ influx surge, reduces ATP production, and postpones the metaphase-anaphase transition and subsequent cell division. These findings provide insight into the mechanisms underlying mitotic energy production and supply required for cell proliferation.

项与 LBR 相关的新闻（医药）

2024-10-04

·生物探索

Cell Reports | 张传茂团队揭示以能量供给为手段的细胞周期调控新机制

引言有丝分裂是细胞周期的关键一环，受到了严格的调控，被认为是高能量需求的一个时期【1】。线粒体对钙离子的摄入可以促进线粒体ATP的瞬时生成，对细胞内能量供给具有重大意义【2】。线粒体对于钙离子的摄入依赖于内质网-线粒体互作位点（ERMCS）。ERMCS是由一些绳索蛋白和线粒体、内质网的外膜蛋白组成的稳定结构，在钙离子传输、脂质合成和线粒体分裂融合等方面发挥着重要的作用【3,4】。当细胞进入有丝分裂期，线粒体和内质网都存在着巨大的变化【5】，这一时期的ERMCS并未被广泛报道。同时，有丝分裂期增长的能量需求是如何供给的也还不清楚。 2024年9月28日，北京大学/昆明理工大学张传茂课题组在Cell Reports杂志上在线发表了题为Mitotic ER-mitochondria contact enhances mitochondrial Ca2+ influx to promote cell division的研究论文。该研究阐明了LBR作为绳索蛋白，在分裂期与VDAC2和IP3R结合，建立起有丝分裂期特异的ERMCS的机制，揭示了LBR介导的ERMCS通过钙流飙升以促进ATP生成，进一步促进了有丝分裂中期到后期转变的机制。研究发现分裂期细胞拥有更高的ATP水平，并与两次线粒体钙离子摄入事件相耦合。其中第二次钙离子摄入主要发生于有丝分裂中期，量大而快，形成钙流飙升，对于细胞周期进程十分关键。阻断钙流飙升会增加有丝分裂中期到后期的用时。有丝分裂期大量增加的ERMCS为钙流飙升提供了物理基础，同时使得有丝分裂期的线粒体拥有更强的钙离子摄入能力。通过对与线粒体相关的内质网膜组分的分离和质谱鉴定，我们发现Lamin B Receptor (LBR)对于有丝分裂期ERMCS的增加起到了关键作用。LBR是一个保守的核膜蛋白，在间期定位于内层核膜；随着核膜崩解，有丝分裂期的LBR融入到内质网上，从面向核质转变为面向胞质，增加了与线粒体互作的可能性【6】。LBR通过跨膜段与VDAC2互作，同时与IP3R互作，建立起有丝分裂期特异性的ERMCS。LBR的缺失导致有丝分裂期ERMCS的数量和线粒体生成的能量减少，但在间期没有变化。LBR的缺失也进一步影响到了细胞周期的进程，延滞了中期到后期的转变。这项工作报道了全新的有丝分裂期特异性ERMCS，揭示了LBR处于有丝分裂期的全新功能，为以能量供给为手段的细胞周期调控机制提供了新的见解。模式图（Credit: Cell Reports）参考文献 https://www-nature-com.libproxy1.nus.edu.sg/articles/d41591-024-00013-5 1. Salazar-Roa, M., and Malumbres, M. (2017). Fueling the Cell Division Cycle. Trends in Cell Biology 27, 69-81. 10.1016/j.tcb.2016.08.009. 2. Zhao, H.X., Li, T., Wang, K., Zhao, F., Chen, J.Y., Xu, G., Zhao, J., Li, T., Chen, L., Li, L., et al. (2019). AMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression. Nature Cell Biology 21, 476-+. 10.1038/s41556-019-0296-3. 3. Prinz, W.A., Toulmay, A., and Balla, T. (2020). The functional universe of membrane contact sites. Nature Reviews Molecular Cell Biology 21, 7-24. 10.1038/s41580-019-0180-9. 4. Rowland, A.A., and Voeltz, G.K. (2012). Endoplasmic reticulum-mitochondria contacts: function of the junction. Nature Reviews Molecular Cell Biology 13, 607-615. 10.1038/nrm3440. 5. Champion, L., Linder, M.I., and Kutay, U. (2017). Cellular Reorganization during Mitotic Entry. Trends in Cell Biology 27, 26-41. 10.1016/j.tcb.2016.07.004. 6. Ma, Y., Cai, S., Lv, Q.L., Jiang, Q., Zhang, Q., Sodmergen, Zhai, Z.H., and Zhang, C.M. (2007). Lamin B receptor plays a role in stimulating nuclear envelope production and targeting membrane vesicles to chromatin during nuclear envelope assembly through direct interaction with importin β. Journal of Cell Science 120, 520-530. 10.1242/jcs.03355. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.celrep.2024.114794 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

临床1期