DOCSLIB.ORG

A Short Evolutionary Journey Across the HERC Ubiquitin Ligases Enrico Bracco2*, Cristina Panuzzo1, Barbara Pergolizzi1* 1Dept

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Short Evolutionary Journey Across the HERC Ubiquitin Ligases Enrico Bracco2*, Cristina Panuzzo1, Barbara Pergolizzi1* 1Dept Bracco E, Panuzzo C, Pergolizzi B. J Immunol Sci. (2018); 2(1): 46-49 Journal of Immunological Sciences Mini Review Open Access A short evolutionary journey across the HERC Ubiquitin Ligases Enrico Bracco2*, Cristina Panuzzo1, Barbara Pergolizzi1* 1Dept. of Clinical & Biological Sciences, University of Turin, Italy 2Dept. of Oncology, University of Turin, Italy Article Info ABSTRACT Article Notes HECT ubiquitin ligases are key components of the eukaryotic ubiquitin- Received: December 22, 2017 proteasome system controlling different cellular physiological aspects as well Accepted: February 05, 2018 as the genesis of several human diseases. Among the HECT family, the HERC *Correspondence: subfamily members are characterized by having one or more RCC1-like domains, Dr. Enrico Bracco, Department of Oncology, University of a C-terminal HECT domain and the molecular mass ranging approximately Turin, AOU S. Luigi, 10043 Orbassano TO, Italy; from 120 kDa to 500 kDa. Due to their large size , some of them are refractory E-mail: [email protected]. to functional characterization. We have recently identified and functionally Dr. Barbara Pergolizzi, Dept. of Clinical & Biological characterized a novel large HECT member in Dictyostelium discoideum that, in Sciences, University of Turin, Italy; many aspects, exhibits structural similarities with the mammalian large HERC1. E-mail: [email protected] In the present minireview , we shortly summarize and revise the current phylogenetic history of HERC proteins among the different living organisms. © 2018 Bracco E. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License. Introduction Ubiquitination, which is the covalent ligation of ubiquitin to a substrate protein, is associated with almost every cellular process including signal transduction, DNA damage repair, cell cycle regulation and autophagic clearance. The process involves three sequential steps each of which is catalysed by a different class dependent way, by the ubiquitin activating enzyme (E1). Afterwards theof enzymes. activated In ubiquitin the first isstep physically the ubiquitin transferred is activated, to the in ubiquitin an ATP- the ubiquitination cascade, catalysing the transfer of ubiquitin from anconjugating E2 enzyme enzyme to form (E2). a Finally, covalent E3 ligbondases with carry a out substrate the final lysinestep in1 (Figure 1). stimulate the ubiquitin transfer either through a direct or an indirectThree mechanism, distinct families named of E3RING lig ases(Really have Interesting been identified, New Gene),which 2 . HECT (Homologous to the E6AP Carboxyl Terminus) and RBR (Ring BetweenIn human Ring) beings RING is the largest family with more than 600 putative members that do not have a direct catalytic role in protein ubiquitination but basically, they act as scaffold facilitating the interaction between E2 and the substrates. In contrast to RING E3 ligases, the HECT and RBR family members catalyse the ubiquitin thentransfer covalently to the substratelinked to throughthe substrate a two-step3,4. HECT reaction: E3s can ubiquitin either is first transferred to a catalytic cysteine residue on the E3 and Page 46 of 49 Bracco E, Panuzzo C, Pergolizzi B. J Immunol Sci. (2018); 2(1): 46-49 Journal of Immunological Sciences of t I) a catalytic HECT domain II) one or more (up to wo conserved domains: 8. HECT is a domain of ~350 localized at their C-terminus and three) RCC1-like domain (RLD) foundamino inacids different firstly species described ranging in Human from yeast Papilloma to humans. Virus (HPV) E6-Associated Protein (E6AP). The HECT domain is Structurally, it consists of two lobes, a larger 9N-terminal- contains(N-lobe) anda crucial a smaller catalytic C-terminal- cysteine (C-lobe) residue lobe and connected interacts by a short flexible linker essential for catalysis . The C-lobe interacts with the E2 enzymes10. Substrates recognition with ubiquitin during the transfer reaction while the N-lobe tois mediatedtheir size byHERC domains members localized have beenwithin catalogued the extended into Figure 1- Schematic representation of the ubiquitin system region N-terminal to the catalytic HECT domain.11 According, but this Ubiquitination proceeds through an initiation step during which the ubiquitin is activated by an E1 enzyme. Then, the activated small (HERC3-6) and large HERC (HERC1-2) ubiquitin is transferred to E2. Selectivity of substrate comes from evolutional considerations. classification is purely operational and not based on the E3 ubiquitin ligases, which couple with E2 to bind substrates The elaboration of a phylogenetic tree with the and catalyse the transfer of the activated ubiquitin from the E2 itself to the substrate. E3 HECT, RING and RBR ligase domains, act sequences of all published animal HECTs from different through different reaction mechanisms. While the E3-HECT ligase catalyses by itself the ubiquitin transfer to the substrate by forming 12. Indeed, the an E3-ubiquitin thioester intermediate, E3-RING ligase domain phylogeneticspecies suggested analysis that established the aforementioned that the small classification and large does not possess direct catalytic activity but rely on the enzymatic HERCwas, subfamiliesto some areextent, only distantlyoversimplified related. In addition, the activity of E2 to ubiquitinate the substrates. Eventually, RBR ligases study allowed to trace the oldest common ancestral HERC combine features of both RING- and HECT-type ligases. Monosiga brevicollis function on their own or in conjunction with accessory whose genome encodes for a small HERC, mostly like the encoding gene in the choanoflagellate or adaptor protein5 mammalian HERC4 and HERC3, but not for canonical large for the substrate recognition for RING E3 ligase is mainly HERC. Animal large HERC members, namely HERC1 and accomplished by . theWhile requirement the selectivity of andmultisubunit specificity HERC1 is structurally characterized by a HECT domain HERC2, are giant proteins with molecular mass ≥500 kDa. region is most likely the sole that serves as the substrate recognitioncomplexes, for domain. the HECT and RBR members the N-terminal localized at its C-terminus and by a single SPRY (spl A moreand Ryanodine composite Receptor),than that ofWD40 HERC1 (G because protein itβ-subunit contains substrate proteins of individual HECT, the physiological like repeats) and two RLDs. The architecture of HERC2 is relevanceDespite ofthe manyefforts madeof these in the interactions identification remain of potential still multiple conserved regions other than the HECT and RLD characterization of HECT E3 members is however available domains, including a Cytb5 (cytochrome b5-like) region, a unclear. Besides the animal kingdom, where the functional only for a handful of them, the evolutionary history of the DOC (DOC1/APC10), a mind-bomb/HERC2 (MIB), a Cullin7 HECT E3s and their biological roles remain still mostly proteinRecently, homology in a (CPH)genetic and suppressor a ZZ-type screeningzinc finger usingdomain. as unknown. In this respect we have recently characterized parental strain a Dictyostelium discoideum a novel large HECT member which might be a functional, mutant13 but not structural, distant relative of the large HERC E3 TORC2 deficient 6,7. In the present minireview, we will attempt to communications we identified, and signal and transduction.functionally characterized,As a matter shortly summarize and revise the long evolutionary history a giant HECT protein regulating some aspects of cell- ofsub-family the HERC E3 ubiquitin ligases members. of fact, this giant E3-ubiquitin ligase6. The controls protein G-protein displays HERC family members structural features and themediated highest cell-to-cell homology signaling to the andhuman acts large as a suppressor HERC1 (57% for domain composition throughout the evolution the TORC2-dependent PKB activity The structurally related HERC E3 ubiquitin ligases the Dictyostelium and the human protein possess a single belong to a subfamily of the HECT E3 family. The HERC similarity and 38% identity within the HECT domain). Both members are proteins of different size (ranging from of several proteins and peculiar of HERC1. Furthermore, theSPRY comparison domain, likely of themediating Dictyostelium protein interaction, typicalitin 100-120 kDa to >500 kDa), characterized by the presence giant E3-ubiqu Page 47 of 49 Bracco E, Panuzzo C, Pergolizzi B. J Immunol Sci. (2018); 2(1): 46-49 Journal of Immunological Sciences a kingdom different from that of an animal as hitherto believed12. Indeed, the vast majority of protists organisms ligase with the human HERC1, shows that the first lacks harbour genes encoding for both putative small and large the RLD whose molecular function in HERC proteins is still HERC. Interestingly, the structural domain composition of andnot fullyguanine understood. releasing Indeed,factor (GRF) RLD1 for domain ARF1, andof the as GEFhuman for HERC1 may act either as a guanine exchange14. On thefactor contrary, (GEF) putative large HERC evokes that of canonical mammalian this biochemical feature is not shared with the structurally the N-terminal region of the vast majority of the protists some Rab family GTPases (Rab3a, Rab5) 15. Additionally, it HERC1 because they possess at least a RLD, SPRY,16. Animalsa single related RLD domain of the small HERCs suchHECT asand the in someurochordate cases, an ( CionaUBA domain intestinalis but all) andof them the has been reported
Load more

Recommended publications
  • The Ubiquitin Conjugating Enzyme: an Important Ubiquitin Transfer Platform in Ubiquitin-Proteasome System
    International Journal of Molecular Sciences Review The Ubiquitin Conjugating Enzyme: An Important Ubiquitin Transfer Platform in Ubiquitin-Proteasome System Weigang Liu 1,2, Xun Tang 2,3, Xuehong Qi 2,3, Xue Fu 2,3, Shantwana Ghimire 1,2, Rui Ma 1, Shigui Li 1, Ning Zhang 3 and Huaijun Si 1,2,3,* 1 College of Agronomy, Gansu Agricultural University, Lanzhou 730070, China; [email protected] (W.L.); [email protected] (S.G.); [email protected] (R.M.); [email protected] (S.L.) 2 Gansu Provincial Key Laboratory of Aridland Crop Science, Gansu Agricultural University, Lanzhou 730070, China; [email protected] (X.T.); [email protected] (X.Q.); [email protected] (X.F.) 3 College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, China; [email protected] * Correspondence: [email protected]; Tel.: +86-931-7631875 Received: 3 March 2020; Accepted: 15 April 2020; Published: 21 April 2020 Abstract: Owing to a sessile lifestyle in nature, plants are routinely faced with diverse hostile environments such as various abiotic and biotic stresses, which lead to accumulation of free radicals in cells, cell damage, protein denaturation, etc., causing adverse effects to cells. During the evolution process, plants formed defense systems composed of numerous complex gene regulatory networks and signal transduction pathways to regulate and maintain the cell homeostasis. Among them, ubiquitin-proteasome pathway (UPP) is the most versatile cellular signal system as well as a powerful mechanism for regulating many aspects of the cell physiology because it removes most of the abnormal and short-lived peptides and proteins.
    [Show full text]
  • Mdm2-Mediated Ubiquitylation: P53 and Beyond
    Cell Death and Differentiation (2010) 17, 93–102 & 2010 Macmillan Publishers Limited All rights reserved 1350-9047/10 $32.00 www.nature.com/cdd Review Mdm2-mediated ubiquitylation: p53 and beyond J-C Marine*,1 and G Lozano2 The really interesting genes (RING)-finger-containing oncoprotein, Mdm2, is a promising drug target for cancer therapy. A key Mdm2 function is to promote ubiquitylation and proteasomal-dependent degradation of the tumor suppressor protein p53. Recent reports provide novel important insights into Mdm2-mediated regulation of p53 and how the physical and functional interactions between these two proteins are regulated. Moreover, a p53-independent role of Mdm2 has recently been confirmed by genetic data. These advances and their potential implications for the development of new cancer therapeutic strategies form the focus of this review. Cell Death and Differentiation (2010) 17, 93–102; doi:10.1038/cdd.2009.68; published online 5 June 2009 Mdm2 is a key regulator of a variety of fundamental cellular has also emerged from recent genetic studies. These processes and a very promising drug target for cancer advances and their potential implications for the development therapy. It belongs to a large family of (really interesting of new cancer therapeutic strategies form the focus of this gene) RING-finger-containing proteins and, as most of its review. For a more detailed discussion of Mdm2 and its other members, Mdm2 functions mainly, if not exclusively, as various functions an interested reader should also consult an E3 ligase.1 It targets various substrates for mono- and/or references9–12. poly-ubiquitylation thereby regulating their activities; for instance by controlling their localization, and/or levels by The p53–Mdm2 Regulatory Feedback Loop proteasome-dependent degradation.
    [Show full text]
  • Application of Microrna Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease
    Article Application of microRNA Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease Jennifer L. Major, Rushita A. Bagchi * and Julie Pires da Silva * Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; [email protected] * Correspondence: [email protected] (R.A.B.); [email protected] (J.P.d.S.) Supplementary Tables Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 www.mdpi.com/journal/mps Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 2 of 25 Table 1. List of all hsa-miRs identified by Human microRNA Disease Database (HMDD; v3.2) analysis. hsa-miRs were identified using the term “genetics” and “circulating” as input in HMDD. Targets CAD hsa-miR-1 Targets IR injury hsa-miR-423 Targets Obesity hsa-miR-499 hsa-miR-146a Circulating Obesity Genetics CAD hsa-miR-423 hsa-miR-146a Circulating CAD hsa-miR-149 hsa-miR-499 Circulating IR Injury hsa-miR-146a Circulating Obesity hsa-miR-122 Genetics Stroke Circulating CAD hsa-miR-122 Circulating Stroke hsa-miR-122 Genetics Obesity Circulating Stroke hsa-miR-26b hsa-miR-17 hsa-miR-223 Targets CAD hsa-miR-340 hsa-miR-34a hsa-miR-92a hsa-miR-126 Circulating Obesity Targets IR injury hsa-miR-21 hsa-miR-423 hsa-miR-126 hsa-miR-143 Targets Obesity hsa-miR-21 hsa-miR-223 hsa-miR-34a hsa-miR-17 Targets CAD hsa-miR-223 hsa-miR-92a hsa-miR-126 Targets IR injury hsa-miR-155 hsa-miR-21 Circulating CAD hsa-miR-126 hsa-miR-145 hsa-miR-21 Targets Obesity hsa-mir-223 hsa-mir-499 hsa-mir-574 Targets IR injury hsa-mir-21 Circulating IR injury Targets Obesity hsa-mir-21 Targets CAD hsa-mir-22 hsa-mir-133a Targets IR injury hsa-mir-155 hsa-mir-21 Circulating Stroke hsa-mir-145 hsa-mir-146b Targets Obesity hsa-mir-21 hsa-mir-29b Methods Protoc.
    [Show full text]
  • 35Th International Society for Animal Genetics Conference 7
    35th INTERNATIONAL SOCIETY FOR ANIMAL GENETICS CONFERENCE 7. 23.16 – 7.27. 2016 Salt Lake City, Utah ABSTRACT BOOK https://www.asas.org/meetings/isag2016 INVITED SPEAKERS S0100 – S0124 https://www.asas.org/meetings/isag2016 epigenetic modifications, such as DNA methylation, and measuring different proteins and cellular metab- INVITED SPEAKERS: FUNCTIONAL olites. These advancements provide unprecedented ANNOTATION OF ANIMAL opportunities to uncover the genetic architecture GENOMES (FAANG) ASAS-ISAG underlying phenotypic variation. In this context, the JOINT SYMPOSIUM main challenge is to decipher the flow of biological information that lies between the genotypes and phe- notypes under study. In other words, the new challenge S0100 Important lessons from complex genomes. is to integrate multiple sources of molecular infor- T. R. Gingeras* (Cold Spring Harbor Laboratory, mation (i.e., multiple layers of omics data to reveal Functional Genomics, Cold Spring Harbor, NY) the causal biological networks that underlie complex traits). It is important to note that knowledge regarding The ~3 billion base pairs of the human DNA rep- causal relationships among genes and phenotypes can resent a storage devise encoding information for be used to predict the behavior of complex systems, as hundreds of thousands of processes that can go on well as optimize management practices and selection within and outside a human cell. This information is strategies. Here, we describe a multi-step procedure revealed in the RNAs that are composed of 12 billion for inferring causal gene-phenotype networks underly- nucleotides, considering the strandedness and allelic ing complex phenotypes integrating multi-omics data. content of each of the diploid copies of the genome.
    [Show full text]
  • Kinase SH3 NH2 Cdc42
    A Dissertation The E3 Ligase CHIP Mediates Ubiquitination and Degradation of Mixed Lineage Kinase 3 and Mixed Lineage Kinase 4 Beta by Natalya A. Blessing Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biology _________________________________________ Dr. Deborah Chadee, Committee Chair _________________________________________ Dr. Richard Komuniecki, Committee Member _________________________________________ Dr. Malathi Krishnamurthy, Committee Member _________________________________________ Dr. Frank Pizza, Committee Member _________________________________________ Dr. Don Ronning, Committee Member _________________________________________ Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo May 2015 Copyright 2015, Natalya A. Blessing This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of The E3 Ligase CHIP Mediates Ubiquitination and Degradation of Mixed Lineage Kinase 3 and Mixed Lineage Kinase 4 Beta by Natalya Blessing Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biology The University of Toledo May 2015 The mixed lineage kinases (MLKs) are serine/threonine mitogen-activated protein kinase kinase kinases (MAP3Ks) that modulate the activities of extracellular signal- regulated kinase, c-Jun N-terminal kinase, and p38 signaling pathways. MLK3 plays a pivotal role in cell invasion, tumorigenesis and metastasis. Wild type MLK4 negatively regulates MAPK signaling by possibly inhibiting MLK3 activation, while mutant MLK4 plays in important role in driving colorectal cancer and glioblastomal tumorigenesis (Martini et al., 2013). The mechanisms by which MLK3 and MLK4 protein levels are regulated in cells are unknown. The carboxyl terminus of HSC-70 interacting protein (CHIP) is a U-box E3 ubiquitin ligase that regulates cytosolic protein degradation in response to stress.
    [Show full text]
  • Pairs of Dipeptides Synergistically Activate the Binding of Substrate by Ubiquitin Ligase Through Dissociation of Its Autoinhibitory Domain
    Pairs of dipeptides synergistically activate the binding of substrate by ubiquitin ligase through dissociation of its autoinhibitory domain Fangyong Du*, Federico Navarro-Garcia†, Zanxian Xia, Takafumi Tasaki, and Alexander Varshavsky‡ Division of Biology, California Institute of Technology, Pasadena, CA 91125 Contributed by Alexander Varshavsky, August 29, 2002 Protein degradation by the ubiquitin (Ub) system controls the con- S. cerevisiae N-end rule pathway is the control of peptide import centrations of many regulatory proteins. The degradation signals through regulated degradation of the 35-kDa homeodomain pro- (degrons) of these proteins are recognized by the system’s Ub ligases tein CUP9, a transcriptional repressor of the di- and tripeptide (complexes of E2 and E3 enzymes). Two substrate-binding sites of transporter PTR2 (13, 24, 25). CUP9 contains an internal (C UBR1, the E3 of the N-end rule pathway in the yeast Saccharomyces terminus-proximal) degron which is recognized by a third substrate- cerevisiae, recognize basic (type 1) and bulky hydrophobic (type 2) binding site of UBR1. Previous work (13) has shown that the N-terminal residues of proteins or short peptides. A third substrate- UBR1-dependent degradation of CUP9 is allosterically activated by binding site of UBR1 targets CUP9, a transcriptional repressor of the dipeptides with destabilizing N-terminal residues. In the resulting peptide transporter PTR2, through an internal (non-N-terminal) de- positive feedback, imported dipeptides bind to UBR1 and accel- gron of CUP9. Previous work demonstrated that dipeptides with erate the UBR1-dependent degradation of CUP9, thereby dere- destabilizing N-terminal residues allosterically activate UBR1, leading pressing the expression of PTR2 and increasing the cell’s capacity to accelerated in vivo degradation of CUP9 and the induction of PTR2 to import peptides (13).
    [Show full text]
  • Post-Translational Modification of OCT4 in Breast Cancer Tumorigenesis
    Cell Death & Differentiation (2018) 25:1781–1795 https://doi.org/10.1038/s41418-018-0079-6 ARTICLE Post-translational modification of OCT4 in breast cancer tumorigenesis 1,2 1,2 3 1,2 1,2 4 5 Yunhee Cho ● Hyeok Gu Kang ● Seok-Jun Kim ● Seul Lee ● Sujin Jee ● Sung Gwe Ahn ● Min Jueng Kang ● 6,7 7 5 1,2 Joon Seon Song ● Joon-Yong Chung ● Eugene C. Yi ● Kyung-Hee Chun Received: 10 June 2017 / Revised: 8 January 2018 / Accepted: 24 January 2018 / Published online: 6 March 2018 © The Author(s) 2018. This article is published with open access Abstract Recurrence and drug resistance of breast cancer are still the main reasons for breast cancer-associated deaths. Cancer stem cell (CSC) model has been proposed as a hypothesis for the lethality of breast cancer. Molecular mechanisms underlying CSC maintenance are still unclear. In this study, we generated mammospheres derived from breast cancer MDA-MB231 cells and MCF7 cells to enrich CSCs and performed DNA microarray analysis. We found that the expression of carboxy terminus of HSP70-interacting protein (CHIP) E3 ubiquitin ligase was significantly downregulated in breast CSCs. CHIP depletion increased mammosphere formation, whereas CHIP overexpression reversed this effect. We identified interactomes 1234567890();,: by mass spectrometry and detected CHIP directly interacted with OCT4, a stemness factor. CHIP overexpression decreased OCT4 stability through proteasomal degradation. CHIP induced OCT4 ubiquitination, whereas H260Q, a catalytic CHIP mutant, did not. Interestingly, we determined that OCT4 was ubiquitinated at lysine 284, and CHIP overexpression did not degrade K284R mutant OCT4. CHIP overexpression decreased the proliferation and side population of breast cancer cells, but these were not occurred in K284R mutant OCT4 overexpressed cells.
    [Show full text]
  • Conserved and Unique Roles of Chaperone-Dependent E3 Ubiquitin Ligase CHIP in Plants
    fpls-12-699756 July 3, 2021 Time: 17:33 # 1 REVIEW published: 09 July 2021 doi: 10.3389/fpls.2021.699756 Conserved and Unique Roles of Chaperone-Dependent E3 Ubiquitin Ligase CHIP in Plants Yan Zhang, Gengshou Xia and Qianggen Zhu* Department of Landscape and Horticulture, Ecology College, Lishui University, Lishui, China Protein quality control (PQC) is essential for maintaining cellular homeostasis by reducing protein misfolding and aggregation. Major PQC mechanisms include protein refolding assisted by molecular chaperones and the degradation of misfolded and aggregated proteins using the proteasome and autophagy. A C-terminus of heat shock protein (Hsp) 70-interacting protein [carboxy-terminal Hsp70-interacting protein (CHIP)] is a chaperone-dependent and U-box-containing E3 ligase. CHIP is a key molecule in PQC by recognizing misfolded proteins through its interacting chaperones and targeting their degradation. CHIP also ubiquitinates native proteins and plays a regulatory role in other Edited by: cellular processes, including signaling, development, DNA repair, immunity, and aging in Shaojun Dai, metazoans. As a highly conserved ubiquitin ligase, plant CHIP plays an important role in Shanghai Normal University, China response to a broad spectrum of biotic and abiotic stresses. CHIP protects chloroplasts Reviewed by: Deepak Chhangani, by coordinating chloroplast PQC both outside and inside the important photosynthetic University of Florida, United States organelle of plant cells. CHIP also modulates the activity of protein phosphatase 2A Ana Paulina Barba De La Rosa, Instituto Potosino de Investigación (PP2A), a crucial component in a network of plant signaling, including abscisic acid Científica y Tecnológica (IPICYT), (ABA) signaling. In this review, we discuss the structure, cofactors, activities, and Mexico biological function of CHIP with an emphasis on both its conserved and unique roles *Correspondence: in PQC, stress responses, and signaling in plants.
    [Show full text]
  • Cullin 3, a Cellular Scripter of the Non-Proteolytic Ubiquitin Code Katerina Jerabkova, Izabela Sumara
    Cullin 3, a cellular scripter of the non-proteolytic ubiquitin code Katerina Jerabkova, Izabela Sumara To cite this version: Katerina Jerabkova, Izabela Sumara. Cullin 3, a cellular scripter of the non-proteolytic ubiq- uitin code. Seminars in Cell and Developmental Biology, Elsevier, 2019, 93, pp.100 - 110. 10.1016/j.semcdb.2018.12.007. hal-03097585 HAL Id: hal-03097585 https://hal.archives-ouvertes.fr/hal-03097585 Submitted on 5 Jan 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Contents lists available at ScienceDirect Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb Review Cullin 3, a cellular scripter of the non-proteolytic ubiquitin code Katerina Jerabkovaa,b,c,d,e, Izabela Sumaraa,b,c,d,⁎ a Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France b Centre National de la Recherche Scientifique UMR 7104, Strasbourg, France c Institut National de la Santé et de la Recherche Médicale U964, Strasbourg, France d Université de Strasbourg, Strasbourg, France e Institute of Molecular Genetics of the ASCR (IMG), Prague, Czech Republic ARTICLE INFO ABSTRACT Keywords: Cullin-RING ubiquitin ligases (CRLs) represent the largest family of E3 ubiquitin ligases that control most if not Cullin 3 all cellular processes.
    [Show full text]
  • Previously Unknown Role for the Ubiquitin Ligase Ubr1 in Endoplasmic Reticulum-Associated Protein Degradation
    Previously unknown role for the ubiquitin ligase Ubr1 in endoplasmic reticulum-associated protein degradation Alexandra Stolz1, Stefanie Besser, Heike Hottmann, and Dieter H. Wolf1 Institut für Biochemie, Universität Stuttgart, 70569 Stuttgart, Germany Edited by Aaron Jehuda Ciechanover, Technion-Israel Institute of Technology, Bat Galim, Haifa, Israel, and approved August 5, 2013 (received for review March 15, 2013) Quality control and degradation of misfolded proteins are essen- substrate. It was thought that this might be the result of a com- tial processes of all cells. The endoplasmic reticulum (ER) is the plementary effect of the remaining ligase, which takes over part entry site of proteins into the secretory pathway in which protein of the ubiquitination activity of the missing ligase (15, 17, 18). folding occurs and terminally misfolded proteins are recognized However, even in the few cases in which the fate of a substrate was and retrotranslocated across the ER membrane into the cytosol. analyzed in strains missing both ligases, Hrd1/Der3 and Doa10, no Here, proteins undergo polyubiquitination by one of the mem- complete cessation of degradation could be observed, indicating brane-embedded ubiquitin ligases, in yeast Hrd1/Der3 (HMG-CoA an additional unknown degradation route (17–19). reductase degradation/degradation of the ER) and Doa10 (degra- Here, we report that the cytosolic ubiquitin ligase Ubr1 functions dation of alpha), and are degraded by the proteasome. In this as an additional E3 ligase in ERAD in yeast. We show that in the study, we identify cytosolic Ubr1 (E3 ubiquitin ligase, N-recognin) as absence of the two canonical polytopic ER membrane ligases, Ubr1 an additional ubiquitin ligase that can participate in ER-associated can provide ubiquitin ligation activity for the ERAD substrate Ste6* protein degradation (ERAD) in yeast.
    [Show full text]
  • The E3 Ubiquitin-Protein Ligase Cullin 3 Regulates HIV-1 Transcription
    cells Article The E3 Ubiquitin-Protein Ligase Cullin 3 Regulates HIV-1 Transcription 1,2, 1, 3,4, 1,5 6,7,8 Simon Langer y , Xin Yin y , Arturo Diaz y , Alex J. Portillo , David E. Gordon , Umu H. Rogers 1,9, John M. Marlett 4, Nevan J. Krogan 6,7,8, John A. T. Young 10, Lars Pache 1,* and Sumit K. Chanda 1,* 1 Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; [email protected] (S.L.); [email protected] (X.Y.); [email protected] (A.J.P.); [email protected] (U.H.R.) 2 Boehringer Ingelheim Pharma GmbH & Co. KG, 55216 Ingelheim am Rhein, Germany 3 Department of Biology, La Sierra University, Riverside, CA 92515, USA; [email protected] 4 The Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; [email protected] 5 Atara Biotherapeutics, Inc., Thousand Oaks, CA 91320, USA 6 Department of Cellular & Molecular Pharmacology, University of California, San Francisco, CA 94143, USA; [email protected] (D.E.G.); [email protected] (N.J.K.) 7 Gladstone Institutes, San Francisco, CA 94158, USA 8 Quantitative Biosciences Institute (QBI), San Francisco, CA 94158, USA 9 UC San Diego School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA 10 Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland; [email protected] * Correspondence: [email protected] (L.P.); [email protected] (S.K.C.); Tel.: +1-(858)-646-3100 (L.P.
    [Show full text]
  • The Scfβ-Trcp E3 Ubiquitin Ligase Regulates Immune Receptor
    The SCFβ-TrCP E3 Ubiquitin Ligase Regulates Immune Receptor Signaling by Targeting the Negative Regulatory Protein TIPE2 This information is current as of September 27, 2021. Yunwei Lou, Meijuan Han, Yaru Song, Jiateng Zhong, Wen Zhang, Youhai H. Chen and Hui Wang J Immunol published online 18 March 2020 http://www.jimmunol.org/content/early/2020/03/17/jimmun ol.1901142 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2020/03/17/jimmunol.190114 Material 2.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 27, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2020 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published March 18, 2020, doi:10.4049/jimmunol.1901142 The Journal of Immunology The SCFb-TrCP E3 Ubiquitin Ligase Regulates Immune Receptor Signaling by Targeting the Negative Regulatory Protein TIPE2 Yunwei Lou,*,† Meijuan Han,*,† Yaru Song,‡ Jiateng Zhong,x Wen Zhang,† Youhai H. Chen,{ and Hui Wang*,† TNFAIP8-like 2 (TIPE2) is a negative regulator of immune receptor signaling that maintains immune homeostasis.
    [Show full text]