更新于：2024-09-19

PACS2

更新于：2024-09-19

基本信息

别名

KIAA0602、PACS-2、PACS1-like protein

+ [3]

简介

Multifunctional sorting protein that controls the endoplasmic reticulum (ER)-mitochondria communication, including the apposition of mitochondria with the ER and ER homeostasis. In addition, in response to apoptotic inducer, translocates BIB to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated BID, the release of cytochrome c, the activation of caspase-3 thereby causing cell death. May also be involved in ion channel trafficking, directing acidic cluster-containing ion channels to distinct subcellular compartments.

关联

100 项与 PACS2 相关的临床结果

登录后查看更多信息

100 项与 PACS2 相关的转化医学

登录后查看更多信息

0 项与 PACS2 相关的专利（医药）

登录后查看更多信息

项与 PACS2 相关的文献（医药）

2024-12-31·Emerging Microbes & Infections

The PACS-2 protein and trafficking motifs in CCHFV Gn and Gc cytoplasmic domains govern CCHFV assembly

Article

作者: Legros, Vincent ; Freitas, Natalia ; Lotteau, Vincent ; Gautam, Anupriya ; Amirache, Fouzia ; Canus, Lola ; Lerolle, Solène ; Mathieu, Cyrille ; Boson, Bertrand ; Cosset, François-Loïc ; Lalande, Alexandre ; Ritter, Maureen

The Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne bunyavirus that causes high mortality in humans. This enveloped virus harbors two surface glycoproteins (GP), Gn and Gc, that are released by processing of a glycoprotein precursor complex whose maturation takes place in the ER and is completed through the secretion pathway. Here, we characterized the trafficking network exploited by CCHFV GPs during viral assembly, envelopment, and/or egress. We identified membrane trafficking motifs in the cytoplasmic domains (CD) of CCHFV GPs and addressed how they impact these late stages of the viral life cycle using infection and biochemical assays, and confocal microscopy in virus-producing cells. We found that several of the identified CD motifs modulate GP transport through the retrograde trafficking network, impacting envelopment and secretion of infectious particles. Finally, we identified PACS-2 as a crucial host factor contributing to CCHFV GPs trafficking required for assembly and release of viral particles.

2024-05-03·Autophagy

Did mitophagy follow the origin of mitochondria?

Review

作者: Degli Esposti, Mauro

Mitophagy is the process of selective autophagy that removes superfluous and dysfunctional mitochondria. Mitophagy was first characterized in mammalian cells and is now recognized to follow several pathways including basal forms in specific organs. Mitophagy pathways are regulated by multiple, often interconnected factors. The present review aims to streamline this complexity and evaluate common elements that may define the evolutionary origin of mitophagy. Key issues surrounding mitophagy signaling at the mitochondrial surface may fundamentally derive from mitochondrial membrane dynamics. Elements of such membrane dynamics likely originated during the endosymbiosis of the alphaproteobacterial ancestor of our mitochondria but underwent an evolutionary leap forward in basal metazoa that determined the currently known variations in mitophagy signaling.Abbreviations: AGPAT, 1-acylglycerol-3-phosphate O-acyltransferase; ATG, autophagy related; BCL2L13, BCL2 like 13; BNIP3, BCL2 interacting protein 3; BNIP3L, BCL2 interacting protein 3 like; CALCOCO, calcium binding and coiled-coil domain; CL, cardiolipin; ER, endoplasmic reticulum; ERMES, ER-mitochondria encounter structure; FBXL4, F-box and leucine rich repeat protein 4; FUNDC1, FUN14 domain containing 1; GABARAPL1, GABA type A receptor associated protein like 1; HIF, hypoxia inducible factor; IMM, inner mitochondrial membrane; LBPA/BMP, lysobisphosphatidic acid; LIR, LC3-interacting region; LPA, lysophosphatidic acid; MAM, mitochondria-associated membranes; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MCL, monolysocardiolipin; ML, maximum likelihood; NBR1, NBR1 autophagy cargo receptor; OMM, outer mitochondrial membrane; PA, phosphatidic acid; PACS2, phosphofurin acidic cluster sorting protein 2; PC/PLC, phosphatidylcholine; PE, phosphatidylethanolamine; PHB2, prohibitin 2; PINK1, PTEN induced kinase 1; PtdIns, phosphatidylinositol; SAR, Stramenopiles, Apicomplexa and Rhizaria; TAX1BP1, Tax1 binding protein 1; ULK1, unc-51 like autophagy activating kinase 1; VDAC/porin, voltage dependent anion channel.

2024-04-01·Protein Science

Inhibitory protein–protein interactions of the SIRT1 deacetylase are choreographed by post‐translational modification

Article

作者: Thompson, Lariah ; DeHaven, Christopher ; Jurczak, Michael ; Thomas, Laurel ; Choi, You-Jin ; Ponticelli, Ryan ; Kim, Yong Joon ; Sipula, Ian ; Krzysiak, Troy C ; Thomas, Gary ; Yang, Yunhan ; Kemper, Jongsook Kim ; Mermigos, Mara M ; Marquez, Andrea ; Gronenborn, Angela M

AbstractRegulation of SIRT1 activity is vital to energy homeostasis and plays important roles in many diseases. We previously showed that insulin triggers the epigenetic regulator DBC1 to prime SIRT1 for repression by the multifunctional trafficking protein PACS‐2. Here, we show that liver DBC1/PACS‐2 regulates the diurnal inhibition of SIRT1, which is critically important for insulin‐dependent switch in fuel metabolism from fat to glucose oxidation. We present the x‐ray structure of the DBC1 S1‐like domain that binds SIRT1 and an NMR characterization of how the SIRT1 N‐terminal region engages DBC1. This interaction is inhibited by acetylation of K112 of DBC1 and stimulated by the insulin‐dependent phosphorylation of human SIRT1 at S162 and S172, catalyzed sequentially by CK2 and GSK3, resulting in the PACS‐2‐dependent inhibition of nuclear SIRT1 enzymatic activity and translocation of the deacetylase in the cytoplasm. Finally, we discuss how defects in the DBC1/PACS‐2‐controlled SIRT1 inhibitory pathway are associated with disease, including obesity and non‐alcoholic fatty liver disease.

项与 PACS2 相关的新闻（医药）

2024-03-21

·生物谷

浙江大学研究者们揭示了治疗糖尿病肾病的关键信号轴

该研究确定了MAPK1-PACS-2轴是治疗靶点的关键途径，并为DKD的发病机制提供了新的见解。糖尿病肾病(DKD)是糖尿病最常见的微血管并发症之一，是终末期肾病(ESRD)的主要病因。在发达国家，大约50%的DKD患者进展为ESRD，导致重大的社会和医疗负担。然而，DKD的致病机制尚不清楚。图片来源：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38169625/ 近日，来自浙江大学的研究者们在Int. J. Biol. Sci.杂志上发表了题为“MAPK1 Mediates MAM Disruption and Mitochondrial Dysfunction in Diabetic Kidney Disease via the PACS-2-Dependent Mechanism”的文章，该研究确定了MAPK1-PACS-2轴是治疗靶点的关键途径，并为DKD的发病机制提供了新的见解。 MAM是由一系列具有不同功能的蛋白质组成的动态连接。MAM蛋白的破坏可能会损害其结构和功能。磷酸氟酸簇分选蛋白2 (phosphofurin酸性簇分选蛋白2,PACS-2)是第一个被发现的MAM驻留蛋白，是MAM的关键调节因子。近期研究发现PACS-2主要在肾小管中表达，高糖会下调其表达。敲低Pacs-2可导致糖尿病小鼠肾小管MAM完整性破坏和线粒体功能障碍，提示Pacs-2在维持DKD中MAM的稳定性中起关键作用。然而，高糖诱导的DKD中PACS-2缺失的机制尚不清楚。在这里，研究者检查了糖尿病人和小鼠的肾脏，以及暴露于高葡萄糖的HK-2细胞，表明高葡萄糖破坏线粒体相关的内质网膜(MAM)并导致线粒体断裂。研究发现，高葡萄糖条件增加了丝裂原活化蛋白激酶1(MAPK1)， MAPK1是MAP激酶信号转导途径的一员，进而降低了磷酸氟酸簇分选蛋白2 (PACS-2)的水平，PACS-2是MAM将线粒体连接到内质网的关键成分。mapk1诱导的MAM破坏导致线粒体断裂，但这可以通过增加PACS-2水平在HK-2细胞中获救。糖尿病小鼠的功能研究表明，抑制MAPK1可增加PACS-2，防止MAM的丢失和线粒体断裂。在高糖刺激的HK-2细胞中，PACS-2过表达可防止MAPK1过表达诱导的MAM破坏和线粒体功能障碍图片来源：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38169625/ 综上所述，本研究确定了MAPK1在MAM中的定位。在患有糖尿病的情况下，MAM中的MAPK1被激活，通过下调PACS-2的表达导致MAM完整性破坏和线粒体功能障碍，提示MAPK1/PACS-2信号通路在MAM中具有功能性。（生物谷 Bioon.com）参考文献 Shanshan Liu et al. MAPK1 Mediates MAM Disruption and Mitochondrial Dysfunction in Diabetic Kidney Disease via the PACS-2-Dependent Mechanism. Int J Biol Sci. 2024 Jan 1;20(2):569-584. doi: 10.7150/ijbs.89291.