更新于：2024-11-01

ATP11B

更新于：2024-11-01

基本信息

别名

ATP11B、ATPase class VI type 11B、ATPase IR

+ [7]

简介

Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of intracellular membranes (PubMed:30018401). May contribute to the maintenance of membrane lipid asymmetry in endosome compartment (PubMed:30018401).

关联

项与 ATP11B 相关的药物

CN118217404

专利挖掘

靶点

ATP11B

作用机制-

在研机构

上海大学

原研机构

上海生源华安生物科技有限公司 [+1]

在研适应症

衰老

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 ATP11B 相关的临床结果

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100 项与 ATP11B 相关的转化医学

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0 项与 ATP11B 相关的专利（医药）

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项与 ATP11B 相关的文献（医药）

2024-12-01·Applied Microbiology and Biotechnology

CHO cell engineering via targeted integration of circular miR-21 decoy using CRISPR/RMCE hybrid system

Article

作者: Ghanbari, Samaneh ; Bayat, Hadi ; Mowla, Seyed Javad ; Davami, Fatemeh ; Adibzadeh, Setare ; Barkhordari, Farzaneh ; Amiri, Shahin ; Faghihi, Faezeh

AbstractChinese hamster ovary (CHO) cells, widely acknowledged as the preferred host system for industrial recombinant protein manufacturing, play a crucial role in developing pharmaceuticals, including anticancer therapeutics. Nevertheless, mammalian cell-based biopharmaceutical production methods are still beset by cellular constraints such as limited growth and poor productivity. MicroRNA-21 (miR-21) has a major impact on a variety of malignancies, including glioblastoma multiforme (GBM). However, reduced productivity and growth rate have been linked to miR-21 overexpression in CHO cells. The current study aimed to engineer a recombinant CHO (rCHO) cell using the CRISPR-mediated precise integration into target chromosome (CRIS-PITCh) system coupled with the Bxb1 recombinase-mediated cassette exchange (RMCE) to express a circular miR-21 decoy (CM21D) with five bulged binding sites for miR-21 sponging. Implementing the ribonucleoprotein (RNP) delivery method, a landing pad was inserted into the genome utilizing the CRIS-PITCh technique. Subsequently, the CM21D cassette flanked by Bxb1 attB was then retargeted into the integrated landing pad using the RMCE/Bxb1 system. This strategy raised the targeting efficiency by 1.7-fold, and off-target effects were decreased. The miR-21 target genes (Pdcd4 and Atp11b) noticed a significant increase in expression upon the miR-21 sponging through CM21D. Following the expression of CM21D, rCHO cells showed a substantial decrease in doubling time and a 1.3-fold increase in growth rate. Further analysis showed an increased yield of hrsACE2, a secretory recombinant protein, by 2.06-fold. Hence, we can conclude that sponging-induced inhibition of miR-21 may lead to a growth rate increase that could be linked to increased CHO cell productivity. For industrial cell lines, including CHO cells, an increase in productivity is crucial. The results of our research indicate that CM21D is an auspicious CHO engineering approach.Key points• CHO is an ideal host cell line for producing industrial therapeutics manufacturing, and miR-21 is downregulated in CHO cells, which produce recombinant proteins.• The miR-21 target genes noticed a significant increase in expression upon the miR-21 sponging through CM21D. Additionally, sponging of miR-21 by CM21D enhanced the growth rate of CHO cells.• Productivity and growth rate were increased in CHO cells expressing recombinant hrs-ACE2 protein after CM21D knocking in.Graphical abstract

2022-12-15·Biology Open

A genome-wide CRISPR screen implicates plasma membrane asymmetry in exogenous C6-ceramide toxicity

Article

作者: Lange, Mike ; Olzmann, James A. ; Deol, Kirandeep K. ; Morris, Siti Nur Sarah

ABSTRACTThe bioactive sphingolipid ceramide impacts diverse cellular processes (e.g. apoptosis and cell proliferation) through its effects on membrane dynamics and intracellular signaling pathways. The dysregulation of ceramide metabolism has been implicated in cancer evasion of apoptosis and targeting ceramide metabolism has potential therapeutic benefits as a strategy to kill cancer cells and slow tumor growth. However, the mechanisms of cancer cell resistance to ceramide-mediated cell death are vastly intertwined and incompletely understood. To shed light on this mystery, we performed a genome-wide CRISPR-Cas9 screen to systematically identify regulators of cancer resistance to the soluble short chain ceramide, C6 ceramide (C6-Cer). Our results reveal a complex landscape of genetic modifiers of C6-Cer toxicity, including genes associated with ceramide and sphingolipid metabolism, vesicular trafficking, and membrane biology. Furthermore, we find that loss of the phospholipid flippase subunit TMEM30A impairs the plasma membrane trafficking of its binding partner, the P4-type ATPase ATP11B, and depletion of TMEM30A or ATP11B disrupts plasma membrane asymmetry and promotes resistance to C6-Cer toxicity. Together, our findings provide a resource of genetic modifiers of C6-Cer toxicity and reveal an unexpected role of plasma membrane asymmetry in C6-Cer induced cell death.

2022-11-01·Journal of Biological Chemistry

Two types of type IV P-type ATPases independently re-establish the asymmetrical distribution of phosphatidylserine in plasma membranes

Article

作者: Miyata, Yugo ; Segawa, Katsumori ; Nagata, Shigekazu ; Yamada, Kyoko

Phospholipids are asymmetrically distributed between the lipid bilayer of plasma membranes in which phosphatidylserine (PtdSer) is confined to the inner leaflet. ATP11A and ATP11C, type IV P-Type ATPases in plasma membranes, flip PtdSer from the outer to the inner leaflet, but involvement of other P4-ATPases is unclear. We herein demonstrated that once PtdSer was exposed on the cell surface of ATP11A^-/-ATP11C^-/- mouse T cell line (W3), its internalization to the inner leaflet of plasma membranes was negligible at 15 °C. However, ATP11A^-/-ATP11C^-/- cells internalized the exposed PtdSer at 37 °C, a temperature at which trafficking of intracellular membranes was active. In addition to ATP11A and 11C, W3 cells expressed ATP8A1, 8B2, 8B4, 9A, 9B, and 11B, with ATP8A1 and ATP11B being present at recycling endosomes. Cells deficient in four P4-ATPases (ATP8A1, 11A, 11B, and 11C) (QKO) did not constitutively expose PtdSer on the cell surface but lost the ability to re-establish PtdSer asymmetry within 1 hour, even at 37 °C. The expression of ATP11A or ATP11C conferred QKO cells with the ability to rapidly re-establish PtdSer asymmetry at 15 °C and 37 °C, while cells expressing ATP8A1 or ATP11B required a temperature of 37 °C to achieve this function, and a dynamin inhibitor blocked this process. These results revealed that mammalian cells are equipped with two independent mechanisms to re-establish its asymmetry: the first is a rapid process involving plasma membrane flippases, ATP11A and ATP11C, while the other is mediated by ATP8A1 and ATP11B, which require an endocytosis process.

项与 ATP11B 相关的新闻（医药）

2024-05-10

·今日头条

抑制肿瘤生长！上海大学/上海交大联合发文：发现胶质瘤治疗新的特异性靶点

本文为转化医学网原创，转载请注明出处作者：Jerry 导读： lncrnas调控多种肿瘤的发生和发展。研究人员首次证实LINC00606在胶质母细胞瘤(GBM)患者标本中显著表达，并与不良预后相关。 5月9日，上海大学联合上海交通大学研究人员在期刊《JouRNAl of Experimental & Clinical Cancer Research》上发表了研究论文，题为“LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B”。本研究表明，LINC00606可以作为胶质瘤的特异性生物标志物。此外，LINC00606的敲低可降低胶质瘤细胞的增殖和迁移能力，促进细胞凋亡。同样，体内研究也表明，LINC00606表达降低可抑制肿瘤生长，这意味着LINC00606可能成为治疗胶质瘤的一种新型特异性靶点。 https://jeccr.biomedcentral.com/articles/10.1186/s13046-024-03058-z#Sec27 研究背景 01 随着医学技术和临床治疗指南的进步，在预测胶质母细胞瘤(GBM)的调控分子和优化治疗策略方面取得了进展;但预后仍较差，有效干预GBM进展的靶基因有待进一步探索。目前迫切需要揭示参与胶质瘤进展的潜在分子机制，以期改善治疗。细胞凋亡在肿瘤干预和治疗中的作用已得到临床认可，因为细胞凋亡的异常激活除了会加剧化疗和放疗抵抗外，还会加剧失控的肿瘤发生和发展。因此，探索调控胶质瘤细胞凋亡过程的关键靶点对优化临床治疗策略具有重要意义。长链非编码RNA (LncRNAs)是一种长度超过200个核苷酸的分子，在肿瘤细胞的许多生物学现象中起着重要作用，如免疫反应、癌症的发生和发展。LncRNAs参与多种细胞活动，包括表观遗传、转录和转录后调控。此外，它们被用作分子海绵，通过海绵microRNA (miRNA)来操纵靶基因的表达，从而作为肿瘤抑制因子或促肿瘤因子的调控系统。作为基因表达网络中的关键角色，lncrna与特定蛋白质相互作用，调节癌细胞的稳态，包括增殖、存活、迁移和其他细胞过程。lncrna调控胶质瘤的相关机制仍有待阐明。研究进展 02 在本研究中，研究人员首次揭示LINC00606在GBM中的表达水平显著升高且具有特异性。高表达LINC00606的GBM具有更强的恶性潜能和更差的预后。功能上，LINC00606可以促进胶质瘤细胞的增殖和迁移，降低细胞凋亡率。在分子机制方面，研究人员发现LINC00606主要存在于细胞质中，通过吸附miR-486-3p来促进胶质瘤进展，miR-486-3p的靶基因是TCF12。此外，TCF12在胶质瘤中高度表达，作为转录因子控制LINC00606、PTEN和KLLN的转录。另外，LINC00606与ATP11B结合，参与PI3K/AKT信号通路的调节，降低细胞凋亡水平，从而促进胶质瘤进展。长非编码RNA不仅能调节基因表达，参与信号转导途径，还能调节表观遗传、转录和转录后修饰。长非编码RNA的表达与多种生物学功能密切相关，包括细胞生存、癌症进展和转移。最近的研究表明，长非编码RNA的异常表达与胶质瘤的病理和预后密切相关。长非编码RNA LPP-AS2通过miR-7-5p/EGFR/PI3K/AKT/c-MYC反馈环促进胶质瘤的肿瘤发生。本研究发现，LINC00606在胶质瘤(包括GBM和LGG)中表达丰富，且与不良预后相关，提示LINC00606可作为胶质瘤的特异性生物标志物。此外，敲低LINC00606可减少胶质瘤细胞的增殖和迁移，促进细胞凋亡。同样，体内实验结果也表明，降低LINC00606的表达可以抑制肿瘤的生长，这表明LINC00606可能成为治疗胶质瘤的新的特异性靶点。 LINC00606是GBM的预后危险因素研究结论 03 总之，LINC00606/miR-486-3p/TCF12/ATP11B轴参与GBM进展的调控，主要通过LINC00606吞噬miR-486-3p和靶向结合ATP11B，在转录和转录后水平上发挥肿瘤调控作用。因此，对调控网络LINC00606的研究可能成为治疗GBM的一种新的治疗策略。参考资料： https://jeccr.biomedcentral.com/articles/10.1186/s13046-024-03058-z#Sec27 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

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