O-GlcNAc cycling and the regulation of nucleocytoplasmic dynamics

2017 ◽  
Vol 45 (2) ◽  
pp. 427-436 ◽  
Author(s):  
Moriah Eustice ◽  
Michelle R. Bond ◽  
John A. Hanover
Keyword(s):  
Structural Integrity ◽  
Complex Structure ◽  
Nutrient Sensing ◽  
Nuclear Pore ◽  
Post Translational Modification ◽  
Nucleocytoplasmic Trafficking ◽  
Protein Targets ◽  
Multifunctional Enzymes ◽  
And Function

The dynamic carbohydrate post-translational modification (PTM) O-linked β-N-acetyl glucosamine (O-GlcNAc) is found on thousands of proteins throughout the nucleus and cytoplasm, and rivals phosphorylation in terms of the number of substrates and pathways influenced. O-GlcNAc is highly conserved and essential in most organisms, with disruption of O-GlcNAc cycling linked to diseases ranging from cancer to neurodegeneration. Nuclear pore proteins were the first identified O-GlcNAc-modified substrates, generating intense and ongoing interest in understanding the role of O-GlcNAc cycling in nuclear pore complex structure and function. Recent advances in detecting and altering O-GlcNAcylation levels have provided insights into many mechanisms by which O-GlcNAcylation influences the nucleocytoplasmic localization and stability of protein targets. The emerging view is that the multifunctional enzymes of O-GlcNAc cycling are critical nutrient-sensing components of a complex network of signaling cascades involving multiple PTMs. Furthermore, O-GlcNAc plays a role in maintaining the structural integrity of the nuclear pore and regulating its function as the gatekeeper of nucleocytoplasmic trafficking.

scholarly journals Role of the Ndc1 interaction network in yeast nuclear pore complex assembly and maintenance

2009 ◽  
Vol 185 (3) ◽  
pp. 475-491 ◽  
Author(s):  
Evgeny Onischenko ◽  
Leslie H. Stanton ◽  
Alexis S. Madrid ◽  
Thomas Kieselbach ◽  
Karsten Weis
Keyword(s):  
Nuclear Pore Complex ◽  
Structural Integrity ◽  
Fluorescent Protein ◽  
Interaction Network ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Binding Partners ◽  
Interaction Partners ◽  
Redundant Functions

The nuclear pore complex (NPC) mediates all nucleocytoplasmic transport, yet its structure and biogenesis remain poorly understood. In this study, we have functionally characterized interaction partners of the yeast transmembrane nucleoporin Ndc1. Ndc1 forms a distinct complex with the transmembrane proteins Pom152 and Pom34 and two alternative complexes with the soluble nucleoporins Nup53 and Nup59, which in turn bind to Nup170 and Nup157. The transmembrane and soluble Ndc1-binding partners have redundant functions at the NPC, and disruption of both groups of interactions causes defects in Ndc1 targeting and in NPC structure accompanied by significant pore dilation. Using photoconvertible fluorescent protein fusions, we further show that the depletion of Pom34 in cells that lack NUP53 and NUP59 blocks new NPC assembly and leads to the reversible accumulation of newly made nucleoporins in cytoplasmic foci. Therefore, Ndc1 together with its interaction partners are collectively essential for the biosynthesis and structural integrity of yeast NPCs.

scholarly journals Distinct Basket Nucleoporins roles in Nuclear Pore Function and Gene Expression: Tpr is an integral component of the TREX-2 mRNA export pathway

2019 ◽  
Author(s):  
Vasilisa Aksenova ◽  
Hang Noh Lee ◽  
Alexandra Smith ◽  
Shane Chen ◽  
Prasanna Bhat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Export ◽  
Protein Modification ◽  
Mrna Export ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nucleocytoplasmic Trafficking ◽  
Pore Complexes ◽  
Slow Turnover

AbstractNuclear pore complexes (NPCs) are important for many processes beyond nucleocytoplasmic trafficking, including protein modification, chromatin remodeling, transcription, mRNA processing and mRNA export. The multi-faceted nature of NPCs and the slow turnover of their components has made it difficult to understand the role of basket nucleoporins (Nup153, Nup50 and Tpr) in these diverse processes. To address this question, we used anAuxin-InducedDegron (AID) system to distinguish roles of basket nucleoporins: Loss of individual nucleoporins caused distinct alteration in patterns of nucleocytoplasmic trafficking and gene expression. Importantly, Tpr elimination caused rapid and pronounced changes in transcriptomic profiles within two hours of auxin addition. These changes were dissimilar to shifts observed after loss of Nup153 or Nup50, but closely related to changes after depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, GANP association to NPCs was specifically disrupted upon TPR depletion. Together, our findings demonstrate a unique and pivotal role of Tpr in regulating gene expression through GANP- and/or NXF1-dependent mRNA nuclear export.

scholarly journals Identification the role of mono-ADP-ribosylation in colorectal cancer by integrated Transcriptome analysis

2021 ◽  
Author(s):  
Shuxian Zhang ◽  
Jiale Duan ◽  
Yanping Yang ◽  
Hanjuan Gong ◽  
Yi Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Alternative Splicing ◽  
Enrichment Analysis ◽  
Drug Candidate ◽  
Post Translational Modification ◽  
Lentiviral Infection ◽  
Whole Transcriptome Sequencing ◽  
And Function

Abstract Purpose Our previous study has clarified the carcinogenic properties of arginine-specific mono-ADP ribosyltransferase 1(ART1), which is considered to be a critical post-translational modification that changes the structure and function of proteins and is widely involved in important processes. This study provides, for the first time, a comprehensive insight of transcriptomic analysis for colorectal cancer cells interfered with ART1 silencing by Illumina RNA-Seq and related verification experiments. Methods Lentiviral infection was used to construct a CT-26 cell line that stably knocks down the ART1 gene, a whole transcriptome sequencing technique was performed to identify differentially expressed genes (DEGs). GO and KEGG classification/enrichment analysis and verification experiments were performed to determine the role of ART1 in the progression of colorectal cancer. Results a total of 5552 DEGs, GO function and KEGG pathway with highest enrichment, forms of SNP and diverse splicing patterns were able to be identified. Importantly, knockdown of ART1 affected the occurrence of the splicing of certain key genes related to tumor cell growth, also down-regulated expression of the key gene PTBP1 for alternative splicing. The overall attenuation of the endoplasmic reticulum unfolded protein response (UPR) signaling pathway caused by ART1 inhibition would unbalance UPR signaling, leading to the occurrence of apoptosis to impede tumorigenesis. Conclusion ART1, which clustered in organelles, may promote the development of colorectal cancer by participating in a variety of new mechanisms including endoplasmic reticulum stress regulation, metabolic process or alternative splicing, which may provide a good clinical drug candidate closer to targeted therapy of CRC.

scholarly journals Dunking into the Lipid Bilayer: How Direct Membrane Binding of Nucleoporins Can Contribute to Nuclear Pore Complex Structure and Assembly

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3601
Author(s):  
Mohamed Hamed ◽  
Wolfram Antonin
Keyword(s):  
Nuclear Envelope ◽  
Current Knowledge ◽  
Complex Structure ◽  
Transmembrane Proteins ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Membrane Spanning ◽  
Pore Complexes ◽  
And Function ◽  
Membrane Spanning Domains

Nuclear pore complexes (NPCs) mediate the selective and highly efficient transport between the cytoplasm and the nucleus. They are embedded in the two membrane structure of the nuclear envelope at sites where these two membranes are fused to pores. A few transmembrane proteins are an integral part of NPCs and thought to anchor these complexes in the nuclear envelope. In addition, a number of nucleoporins without membrane spanning domains interact with the pore membrane. Here we review our current knowledge of how these proteins interact with the membrane and how this interaction can contribute to NPC assembly, stability and function as well as shaping of the pore membrane.

scholarly journals Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Vasilisa Aksenova ◽  
Alexandra Smith ◽  
Hangnoh Lee ◽  
Prasanna Bhat ◽  
Caroline Esnault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Export ◽  
Mrna Turnover ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nucleocytoplasmic Trafficking ◽  
Cellular Functions ◽  
Pore Complexes ◽  
Slow Turnover

Abstract Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how individual nucleoporins act in these diverse processes. To address this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins NUP153, NUP50 and TPR. Acute depletion of TPR causes rapid and pronounced changes in transcriptomic profiles. These changes are dissimilar to shifts observed after loss of NUP153 or NUP50, but closely related to changes caused by depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) to NPCs and results in abnormal RNA transcription and export. Our findings demonstrate a unique and pivotal role of TPR in gene expression through TREX-2- and/or NXF1-dependent mRNA turnover.

scholarly journals Transcriptomic Bioinformatic Analyses of Atria Uncover Involvement of Pathways Related to Strain and Post-translational Modification of Collagen in Increased Atrial Fibrillation Vulnerability in Intensely Exercised Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Yena Oh ◽  
Sibao Yang ◽  
Xueyan Liu ◽  
Sayantan Jana ◽  
Farzad Izaddoustdar ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Health ◽  
Venous Pressure ◽  
Post Translational Modification ◽  
Time Points ◽  
Ventricular Structure ◽  
And Function ◽  
Collagen Genes ◽  
Necrosis Factor

Atrial Fibrillation (AF) is the most common supraventricular tachyarrhythmia that is typically associated with cardiovascular disease (CVD) and poor cardiovascular health. Paradoxically, endurance athletes are also at risk for AF. While it is well-established that persistent AF is associated with atrial fibrosis, hypertrophy and inflammation, intensely exercised mice showed similar adverse atrial changes and increased AF vulnerability, which required tumor necrosis factor (TNF) signaling, even though ventricular structure and function improved. To identify some of the molecular factors underlying the chamber-specific and TNF-dependent atrial changes induced by exercise, we performed transcriptome analyses of hearts from wild-type and TNF-knockout mice following exercise for 2 days, 2 or 6 weeks of exercise. Consistent with the central role of atrial stretch arising from elevated venous pressure in AF promotion, all 3 time points were associated with differential regulation of genes in atria linked to mechanosensing (focal adhesion kinase, integrins and cell-cell communications), extracellular matrix (ECM) and TNF pathways, with TNF appearing to play a permissive, rather than causal, role in gene changes. Importantly, mechanosensing/ECM genes were only enriched, along with tubulin- and hypertrophy-related genes after 2 days of exercise while being downregulated at 2 and 6 weeks, suggesting that early reactive strain-dependent remodeling with exercise yields to compensatory adjustments. Moreover, at the later time points, there was also downregulation of both collagen genes and genes involved in collagen turnover, a pattern mirroring aging-related fibrosis. By comparison, twofold fewer genes were differentially regulated in ventricles vs. atria, independently of TNF. Our findings reveal that exercise promotes TNF-dependent atrial transcriptome remodeling of ECM/mechanosensing pathways, consistent with increased preload and atrial stretch seen with exercise. We propose that similar preload-dependent mechanisms are responsible for atrial changes and AF in both CVD patients and athletes.

Post Translational Modification and its pathologic association in Rheumatoid Arthritis: A brief perspective

2021 ◽  
Vol 22 ◽  
Author(s):  
Vishnupreetha Vasudevan ◽  
Prachi Agnihotri ◽  
Sagarika Biswas
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Pain ◽  
Cyclic Peptide ◽  
Delayed Diagnosis ◽  
Living System ◽  
The Body ◽  
Post Translational Modification ◽  
And Function ◽  
Inflammatory Autoimmune Disease

: Post Translational Modification (PTM) is the process in which covalent addition of functional groups on protein happens to maintain their structure, function and stability. Every PTM process in our living system happens to increase the functional diversity of protein. But sometimes it happens without any regulation and occurrence of this specific change in proteins are leading to autoimmunity. Rheumatoid arthritis (RA) is one such chronic, inflammatory, autoimmune disease that affects joints. Proper treatment can be manageable for RA, but it is not completely curable. Delayed diagnosis of RA can cause severe bone pain, stiffness, inflammation, redness in joints and affect other parts of the body such as liver, kidney etc. Early diagnosis of disease is preferable to cure it effectively. Currently, Rheumatoid factor (RF) and anti-citrullinated cyclic peptide (Anti-CCP) are considered as biomarkers to diagnose RA. Other than citrullination several other PTM’s are also involved in generation of autoantibodies such as, carbamylation, glycosylation, glycation, acetylation, ubiquitination, proteolysis, phosphorylation, lipidation. Aim of this review is to elucidate several considerable changes in form, nature and function of above PTMs in RA, affecting joints and day to day life. This review will give a recent overview on the role of PTMs in the pathogenesis of RA, focusing on the modifications.

scholarly journals The role of the integral membrane nucleoporins Ndc1p and Pom152p in nuclear pore complex assembly and function

2006 ◽  
Vol 173 (3) ◽  
pp. 361-371 ◽  
Author(s):  
Alexis S. Madrid ◽  
Joel Mancuso ◽  
W. Zacheus Cande ◽  
Karsten Weis
Keyword(s):  
Electron Microscopy ◽  
Saccharomyces Cerevisiae ◽  
Nuclear Envelope ◽  
Lipid Bilayers ◽  
Nuclear Pore Complex ◽  
Transmembrane Proteins ◽  
Nuclear Pore ◽  
Large Channel ◽  
And Function

The nuclear pore complex (NPC) is a large channel that spans the two lipid bilayers of the nuclear envelope and mediates transport events between the cytoplasm and the nucleus. Only a few NPC components are transmembrane proteins, and the role of these proteins in NPC function and assembly remains poorly understood. We investigate the function of the three integral membrane nucleoporins, which are Ndc1p, Pom152p, and Pom34p, in NPC assembly and transport in Saccharomyces cerevisiae. We find that Ndc1p is important for the correct localization of nuclear transport cargoes and of components of the NPC. However, the role of Ndc1p in NPC assembly is partially redundant with Pom152p, as cells lacking both of these proteins show enhanced NPC disruption. Electron microscopy studies reveal that the absence of Ndc1p and Pom152p results in aberrant pores that have enlarged diameters and lack proteinaceous material, leading to an increased diffusion between the cytoplasm and the nucleus.

Sign in / Sign up

Export Citation Format

Share Document