DOCSLIB.ORG

Supplementary Table 1: Chip-On-Chip Identified Genes to Which Wild-Type and Mutant Htt Are Significantly Bound To. Gene Identifier and Chromosomal Location Are In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplementary Table 1: Chip-On-Chip Identified Genes to Which Wild-Type and Mutant Htt Are Significantly Bound To. Gene Identifier and Chromosomal Location Are In Supplementary Table 1: ChIP-on-chip identified genes to which wild-type and mutant Htt are significantly bound to. Gene identifier and chromosomal location are in 7/7 the left two columns. Some genes are bound only by wild type Htt (STHdh ), some 111/111 exclusively by mutant Htt (STHdh ). A few genes are bound in both cell lines. Gene Chromosome Bound in 7/7 Bound in 111/111 Bound in both 0610006K04Rik chr19 7/7 0610027B03Rik-Kif18a chr2 7/7 0610030I09Rik chr2 111/111 0610040B21Rik chr4 7/7 0710001E13Rik chr9 111/111 1110030J09Rik chr11 7/7 1110031B11Rik chr3 7/7 1110032A13RikTxnl4 chr18 7/7 1110058L19Rik chr1 7/7 1110060O18Rik chr1 7/7 1500011L16Rik chr4 111/111 1600012F09Rik chr13 7/7 1600015H20Rik chr2 111/111 1700001L23Rik chr9 7/7 1700007K09Rik-1700063I17Rik chr7 7/7 1700014P03Rik chr7 111/111 1700020L24Rik chr11 111/111 1700026D08Rik chr7 7/7 111/111 Both 1700034E13Rik chr18 111/111 1700063I17Rik chr7 7/7 1700108M19Rik chr12 7/7 1700111I05Rik chr5 7/7 1810020G14Rik chr12 111/111 1810046J19RikGrb7 chr11 111/111 2010106E10Rik chrX 111/111 2310002B14Rik chr16 7/7 2310009E04Rik chr4 7/7 2310016A09Rik chr15 7/7 111/111 Both 2310016N21Rik chr5 7/7 2310034L04Rik chr17 111/111 2310042G06Rik chr2 111/111 2310045A20Rik chr5 111/111 2310057J18Rik chr10 7/7 2410004A20Rik chr9 7/7 2410042D21Rik chr2 111/111 2410116I05Rik chr4 7/7 2600005O03Rik chr15 7/7 2610014F08Rik chr2 7/7 2610027C15Rik chr4 7/7 2610209N15Rik chr11 7/7 111/111 Both 2610524H06Rik chr5 111/111 2610528M18RikMut chr17 111/111 2700029E10Rik chr14 7/7 2810052M02Rik chr3 7/7 2900016D05Rik chr17 7/7 111/111 Both 3110003A22Rik chr4 111/111 3110023G01Rik chr18 7/7 3930401K13Rik chr16 111/111 4122402O22Rik chr16 7/7 4632422M10Rik chr13 111/111 4831428F09 chr1 7/7 4921504I05Rik chr13 7/7 4921531G14Rik chr15 7/7 4930429A22Rik chr1 111/111 4930444A02Rik chr8 111/111 4930451A13Rik chr16 7/7 4930479M11Rik chr7 7/7 4930486G11Rik chr9 111/111 4930511H01Rik chr1 7/7 4930519N16Rik chr13 7/7 4930522D07Rik chr3 7/7 4930524B15Rik chr11 111/111 4931406I20Rik chr4 7/7 4931406P16Rik chr7 111/111 4931417A20 chr2 111/111 4933409D10Rik chr18 7/7 4933409K07Rik chr4 7/7 111/111 Both 4933417K05Rik chr10 111/111 5330410G16Rik chr8 7/7 6030441H18Rik chr7 111/111 6820429M01 chr7 7/7 9230106L14Rik chr2 7/7 111/111 Both 9430059P22Rik chr14 7/7 9530068E07Rik chr11 111/111 9530090G24Rik chr2 111/111 A630042L21Rik chr18 111/111 A730008L03Rik chr2 7/7 111/111 Both A730017C20Rik chr18 111/111 A830020B06Rik chr1 111/111 A830053O21Rik chr11 7/7 Aadac chr3 7/7 Abca8b chr11 7/7 Abcb11 chr2 7/7 Abcb1a chr5 111/111 Abcc6-Nomo1 chr7 111/111 Acoxl chr2 7/7 Acvrinp1 chr5 111/111 Adam24 chr8 7/7 Adam32 chr8 7/7 Adm chr7 7/7 Adm2 chr15 111/111 AdmrRdh1 chr10 7/7 Agtpbp1 chr13 7/7 Ahi1 chr10 111/111 Ahrr chr13 7/7 Akt1AI132321 chr12 7/7 Aldrl6 chr15 7/7 Alpk3 chr7 111/111 Als2cr3 chr1 7/7 Ambn chr5 111/111 Anapc7 chr5 7/7 Ankrd32 chr13 111/111 Aoc2 chr11 7/7 Apg10l chr13 7/7 Aplp2 chr9 111/111 Arhgap18 chr10 7/7 111/111 Both Armc8Dbr1 chr9 111/111 Arpc1b chr5 111/111 Art5 chr7 7/7 Asahl chr5 111/111 Asb14 chr14 111/111 Asb8 chr15 7/7 Ascl1 chr10 7/7 Asgr2 chr11 7/7 Atp2c1 chr9 7/7 Atrx chrX 7/7 AU018778 chr8 7/7 AW210596 chr19 111/111 B230358A15Rik chrX 7/7 B230399E16Rik chr18 111/111 B3galt5 chr16 111/111 Baat chr4 111/111 Bag2 chr1 7/7 BC018371 chr11 7/7 BC019561 chr18 7/7 BC020188 chr9 7/7 111/111 Both BC021785 chr10 111/111 BC026439 chr15 7/7 BC027057 chr13 7/7 BC032265 chr11 7/7 BC034097 chr11 7/7 111/111 Both BC037674 chr14 7/7 BC066107 chr17 7/7 Bex2 chrX 111/111 Bhlhb9 chrX 111/111 Bicd2 chr13 7/7 111/111 Both Bmpr1b chr3 7/7 Bok chr1 7/7 Brunol4 chr18 111/111 Btc chr5 7/7 Btg3 chr16 7/7 Btg4 chr9 7/7 C130057D23Rik chr4 7/7 C130068O12Rik chr15 7/7 111/111 Both C1ql1 chr11 7/7 C2 chr17 7/7 C230012O17Rik-Gpr63 chr4 7/7 C730014E05Rik chr16 111/111 Cacna1b chr2 7/7 Capn3 chr2 7/7 Caskin2 chr11 7/7 Ccnb1 chr13 7/7 Cd200r3 chr16 7/7 Cd52-D4Bwg1540e chr4 7/7 Cd99l2 chrX 111/111 Cdc91l1 chr2 7/7 Cdh11 chr8 111/111 Cdon chr9 7/7 Centd2 chr7 111/111 Chchd1 chr14 7/7 Chic1 chrX 7/7 chr1:161739566-161739626 chr1 111/111 chr12:109234647109234707 chr12 111/111 chr14:5657693956576999 chr14 111/111 chr16:4283083142830771 chr16 111/111 chr16:7800562678005686 chr16 111/111 chr16:8958744789587507 chr16 7/7 111/111 Both chr17:8460947984609539 chr17 111/111 chrY:15027747-15027687 chrY 7/7 111/111 Both chrY:15027967-15028027 chrY 111/111 chrY:15028307-15028247 chrY 111/111 chrY:15028475-15028535 chrY 7/7 111/111 Both chrY:17146080-17146140 chrY 7/7 111/111 Both chrY:34924552-34924492 chrY 7/7 111/111 Both chrY:3649958-3649898 chrY 111/111 chrY:3650178-3650238 chrY 111/111 chrY:39819170-39819110 chrY 111/111 chrY:41073447-41073387 chrY 7/7 111/111 Both chrY:5814034-5813974 chrY 111/111 Chuk chr19 7/7 Cidec-Jagn1 chr6 111/111 Clca2 chr3 7/7 Clec4a2 chr6 7/7 Clec4d chr6 7/7 111/111 Both Clec9a chr6 7/7 Clu chr14 7/7 Cml1 chr6 111/111 Cntf chr19 7/7 111/111 Both Cpa1 chr6 7/7 Cpa5 chr6 7/7 Cpeb3 chr19 111/111 Cpeb4 chr11 7/7 Crat-Ppp2r4 chr2 111/111 Crbn chr6 7/7 Crisp3 chr17 7/7 Csna chr5 111/111 Csnk chr5 111/111 Cspg5 chr9 7/7 Ctla4 chr1 7/7 Ctps2 chrX 7/7 Cyct-Drbp1 chr2 111/111 Cyp2c29 chr19 7/7 Cyp2c55 chr19 111/111 Cyp2d13 chr15 111/111 Cyp2e1 chr7 7/7 Cyp2j9 chr4 7/7 D10Ertd214eIpmk chr10 111/111 D10Wsu52e chr10 111/111 D12Ertd553e chr12 7/7 D17Ertd288e chr17 7/7 D230005D02Rik chr14 7/7 D330012D11Rik chr11 7/7 111/111 Both D430020F16 chr7 7/7 D4Ertd22e-Fbxo42 chr4 111/111 D630003K02Rik chr7 111/111 D730040F13Rik chr4 7/7 D830007F02Rik chr8 7/7 111/111 Both Dad1Abhd4 chr14 111/111 Ddx26 chr14 111/111 Ddx3y chrY 111/111 Defb14 chr8 111/111 Defb39 chr8 7/7 Dek chr13 7/7 Dnajc2 chr5 111/111 Dncl2b chr8 7/7 Doc2a chr7 7/7 Dpp10 chr1 7/7 111/111 Both Dsg3 chr18 7/7 Dtna chr18 7/7 Dusp13 chr14 111/111 E030025L21Rik chr12 7/7 E130114P18Rik chr4 111/111 Eapa2 chr6 7/7 Eef1a2 chr2 7/7 Elac2 chr11 111/111 Elovl2 chr13 111/111 Elovl3 chr19 7/7 Elovl4 chr9 7/7 Emr1 chr17 7/7 Enam chr5 7/7 Enpp3 chr10 7/7 Ep400 chr5 111/111 Epb4.1l3 chr17 7/7 111/111 Both Epc1 chr18 7/7 Ephx2 chr14 111/111 Epn3 chr11 7/7 Eral1 chr11 111/111 Esco22610528H13Rik chr14 7/7 Evc-Evc2 chr5 111/111 F13a1 chr13 111/111 Fabp7 chr10 111/111 Fbl chr7 7/7 Fbn1 chr2 7/7 111/111 Both Fbxw15 chr9 7/7 Fgb chr3 111/111 Fgf12 chr16 111/111 Fgl2 chr5 7/7 Fkrp chr7 111/111 Fntb chr12 111/111 Foxf1a chr8 111/111 Foxm1 chr6 7/7 Frat1 chr19 7/7 Fshb chr2 111/111 Fshprh1 chrX 7/7 Fv1 chr12 7/7 Gad1 chr2 7/7 Galnt6 chr15 7/7 Gata6 chr18 111/111 Gbp5 chr3 7/7 Gc chr5 7/7 Gcap14 chr14 111/111 Gcgr chr11 7/7 Gchfr chr2 111/111 Gif chr19 111/111 Gjb6 chr14 7/7 Glt25d1 chr8 111/111 Gmfg chr7 7/7 Gnpda2 chr5 7/7 Gpa33 chr1 7/7 Gpm6a chr8 111/111 Gpr128 chr16 111/111 Gpr40 chr7 7/7 111/111 Both Gspt1 chr16 111/111 Gstz1 chr12 7/7 111/111 Both Guca1b chr17 111/111 Gys2 chr6 111/111 Gzmb chr14 111/111 H2 chr17 7/7 H28 chr3 7/7 Hace1 chr10 7/7 Hdhd1a chr18 111/111 Helz chr11 7/7 Hivep1 chr13 7/7 Hlx1 chr1 7/7 111/111 Both Hmmr chr11 7/7 HnrpcRpgrip1 chr14 7/7 Hps6 chr19 7/7 Hrh4 chr18 111/111 Hrpt2 chr1 111/111 Hsd3b1 chr3 7/7 Hspa12a chr19 111/111 Hspb3 chr13 111/111 Hyal3 chr9 111/111 Ibsp chr5 111/111 Ifitm2-Ifitm1 chr7 7/7 Ifna5 chr4 7/7 Ighg chr12 7/7 111/111 Both Il17f chr1 7/7 Il1f5 chr2 111/111 Ipo4 chr14 111/111 Isyna1 chr8 111/111 Itgae chr11 7/7 Itgb3bp chr4 7/7 111/111 Both Jam3 chr9 111/111 Jarid1b chr1 111/111 Junb chr8 7/7 Kbtbd4 chr2 7/7 Kcna7 chr7 7/7 Kcnab2 chr4 7/7 Kera chr10 7/7 111/111 Both Kif22 chr7 111/111 Kif2a chr13 111/111 Klk4 chr7 7/7 Klrc2 chr6 7/7 111/111 Both Klrc3 chr6 111/111 Klrk1 chr6 7/7 111/111 Both Krtap16 chr16 111/111 Krtap21 chr16 111/111 Lancl3 chrX 111/111 Lao1 chr4 7/7 111/111 Both Lass1 chr8 111/111 Liph chr16 7/7 Lipl2 chr19 7/7 Lmo2 chr2 7/7 LOC382133 chrY 7/7 LOC432534 chr11 7/7 111/111 Both LOC433332 chr1 7/7 Lrrc21 chr14 7/7 Lrrc5 chr5 7/7 Ltbp1 chr17 111/111 Lum chr10 7/7 Mad chr6 111/111 Mad2l1bp chr17 111/111 Mag chr7 7/7 Magoh chr4 111/111 Man2b1 chr8 7/7 Mapk8 chr14 111/111 Matn2 chr15 7/7 Mb chr15 7/7 Mbl1 chr14 7/7 Meig1-Dclre1c chr2 7/7 Meox2 chr12 7/7 Mfap4 chr11 7/7 MGC54654 chr15 7/7 Mgea6 chr12 7/7 Mgst1 chr6 111/111 Mib1 chr18 7/7 111/111 Both Mid1 chrX 7/7 Mmp10 chr9 7/7 Mmp1a chr9 7/7 111/111 Both Mobkl2b chr4 7/7 Mobkl2c chr4 7/7 111/111 Both Mog chr17 7/7 MOR118 chr14 7/7 Morc chr16 7/7 Mpl chr4 7/7 Mpp5 chr12 7/7 Mrgprb4 chr7 111/111 Mrpl16 chr19 7/7 Mrpl27 chr11 7/7 111/111 Both Ms4a7 chr19 7/7 Mtpn chr6 111/111 Muc10 chr5 7/7 111/111 Both Mup4 chr4 111/111 Mustn1 chr14 111/111 Mybpc3 chr2 7/7 Myl2 chr5 111/111 Myo1g chr11 7/7 Myo7a chr7 7/7 111/111 Both Naca chr10 7/7 Nalp4b chr7 111/111 Nalp5 chr7 7/7 Narg1lMtrf1 chr14 7/7 Ndufs6Mrpl36 chr13 7/7 Nedd8 chr14 111/111 Neto1 chr18 7/7 111/111 Both Neurod2 chr11 7/7 Nf1 chr11 7/7 111/111 Both Nkx1 chr7 111/111 Nol6 chr4 111/111 Nola2 chr11 7/7 Notch1 chr2 7/7 Npr1-Ilf2 chr3 7/7 Nr1d1 chr11 7/7 Nr1i2Popdc2 chr16 111/111 Nrbp chr5 7/7 Nrip3 chr7 111/111 Nsf chr11 111/111 Nudt1 chr5 111/111 Nudt7 chr8 111/111 Nxf2 chrX 7/7 Olfr1036 chr2 111/111 Olfr108 chr17 111/111 Olfr1094 chr2 111/111 Olfr11 chr13 7/7 111/111 Both Olfr1123 chr2 7/7 111/111 Both Olfr1138-Olfr1140 chr2 111/111 Olfr1176 chr2 7/7 Olfr1183 chr2 7/7 111/111 Both Olfr1184 chr2 111/111 Olfr129 chr17 111/111 Olfr1324 chrX 7/7 Olfr134 chr17 111/111 Olfr1370 chr13 7/7 Olfr139 chr11 111/111 Olfr1406 chr1 7/7 Olfr1426 chr19 7/7 Olfr1433 chr19 7/7 Olfr1440 chr19 7/7 Olfr1457 chr19 7/7 Olfr1509 chr14 111/111 Olfr1510 chr14 7/7 Olfr164 chr16 7/7 Olfr166 chr16 111/111 Olfr168 chr16 7/7 Olfr181 chr16 111/111 Olfr187 chr16
Load more

Recommended publications
  • The HECT Domain Ubiquitin Ligase HUWE1 Targets Unassembled Soluble Proteins for Degradation
    OPEN Citation: Cell Discovery (2016) 2, 16040; doi:10.1038/celldisc.2016.40 ARTICLE www.nature.com/celldisc The HECT domain ubiquitin ligase HUWE1 targets unassembled soluble proteins for degradation Yue Xu1, D Eric Anderson2, Yihong Ye1 1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; 2Advanced Mass Spectrometry Core Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA In eukaryotes, many proteins function in multi-subunit complexes that require proper assembly. To maintain complex stoichiometry, cells use the endoplasmic reticulum-associated degradation system to degrade unassembled membrane subunits, but how unassembled soluble proteins are eliminated is undefined. Here we show that degradation of unassembled soluble proteins (referred to as unassembled soluble protein degradation, USPD) requires the ubiquitin selective chaperone p97, its co-factor nuclear protein localization protein 4 (Npl4), and the proteasome. At the ubiquitin ligase level, the previously identified protein quality control ligase UBR1 (ubiquitin protein ligase E3 component n-recognin 1) and the related enzymes only process a subset of unassembled soluble proteins. We identify the homologous to the E6-AP carboxyl terminus (homologous to the E6-AP carboxyl terminus) domain-containing protein HUWE1 as a ubiquitin ligase for substrates bearing unshielded, hydrophobic segments. We used a stable isotope labeling with amino acids-based proteomic approach to identify endogenous HUWE1 substrates. Interestingly, many HUWE1 substrates form multi-protein com- plexes that function in the nucleus although HUWE1 itself is cytoplasmically localized. Inhibition of nuclear entry enhances HUWE1-mediated ubiquitination and degradation, suggesting that USPD occurs primarily in the cytoplasm.
    [Show full text]
  • A Family of Mammalian E3 Ubiquitin Ligases That Contain the UBR Box Motif and Recognize N-Degrons Takafumi Tasaki,1 Lubbertus C
    MOLECULAR AND CELLULAR BIOLOGY, Aug. 2005, p. 7120–7136 Vol. 25, No. 16 0270-7306/05/$08.00ϩ0 doi:10.1128/MCB.25.16.7120–7136.2005 Copyright © 2005, American Society for Microbiology. All Rights Reserved. A Family of Mammalian E3 Ubiquitin Ligases That Contain the UBR Box Motif and Recognize N-Degrons Takafumi Tasaki,1 Lubbertus C. F. Mulder,2 Akihiro Iwamatsu,3 Min Jae Lee,1 Ilia V. Davydov,4† Alexander Varshavsky,4 Mark Muesing,2 and Yong Tae Kwon1* Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 152611; Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 100162; Protein Research Network, Inc., Yokohama, Kanagawa 236-0004, Japan3; and Division of Biology, California Institute of Technology, Pasadena, California 911254 Received 15 March 2005/Returned for modification 27 April 2005/Accepted 13 May 2005 A subset of proteins targeted by the N-end rule pathway bear degradation signals called N-degrons, whose determinants include destabilizing N-terminal residues. Our previous work identified mouse UBR1 and UBR2 as E3 ubiquitin ligases that recognize N-degrons. Such E3s are called N-recognins. We report here that while double-mutant UBR1؊/؊ UBR2؊/؊ mice die as early embryos, the rescued UBR1؊/؊ UBR2؊/؊ fibroblasts still retain the N-end rule pathway, albeit of lower activity than that of wild-type fibroblasts. An affinity assay for proteins that bind to destabilizing N-terminal residues has identified, in addition to UBR1 and UBR2, a huge (570 kDa) mouse protein, termed UBR4, and also the 300-kDa UBR5, a previously characterized mammalian E3 known as EDD/hHYD.
    [Show full text]
  • The Ubiquitin Proteasome System and Its Involvement in Cell Death Pathways
    Cell Death and Differentiation (2010) 17, 1–3 & 2010 Macmillan Publishers Limited All rights reserved 1350-9047/10 $32.00 www.nature.com/cdd Editorial The ubiquitin proteasome system and its involvement in cell death pathways F Bernassola1, A Ciechanover2 and G Melino1,3 Cell Death and Differentiation (2010) 17, 1–3; doi:10.1038/cdd.2009.189 Following the awarding of the 2004 Nobel Prize in Chemistry Inactivation of the proteasome following caspase-mediated to Aaron Ciechanover, Avram Hershko, and Irwin A Rose cleavage may disable the proteasome, interfering with its for the discovery of ubiquitin (Ub)-mediated degradation, role in the regulation of key cellular processes and thereby Cell Death and Differentiation has drawn the attention of facilitating induction of apoptosis. The noted recent develop- its readers to the Ub Proteasome System (UPS) and its ments show how understanding of these functions is just involvement in regulating cell death pathways.1–4 The current starting to emerge. For example, why does dIAP1 associate set of reviews is an update on this theme.5–16 with multiple E2s via its RING finger? Does dIAP1 also interact From previous review articles published in Cell Death and with the E3 – the F-box protein Morgue, which is a part of an Differentiation, it was apparent that the UPS has a major SCF E3 complex? Why does dIAP1, which is an E3, have to mechanistic role in regulating cell death via modification and interact with other ligases such as the N-end rule UBR1 and degradation of key regulatory proteins involved in
    [Show full text]
  • TRAIP Modulates the IGFBP3/AKT Pathway to Enhance the Invasion
    www.nature.com/cddis ARTICLE OPEN TRAIP modulates the IGFBP3/AKT pathway to enhance the invasion and proliferation of osteosarcoma by promoting KANK1 degradation ✉ ✉ Mi Li1,6, Wei Wu2,6, Sisi Deng3, Zengwu Shao2 and Xin Jin 4,5 © The Author(s) 2021 Osteosarcoma is one of the most common primary malignancies in bones and is characterized by high metastatic rates. Circulating tumor cells (CTCs) derived from solid tumors can give rise to metastatic lesions, increasing the risk of death in patients with cancer. Here, we used bioinformatics tools to compare the gene expression between CTCs and metastatic lesions in osteosarcoma to identify novel molecular mechanisms underlying osteosarcoma metastasis. We identified TRAIP as a key differentially expressed gene with prognostic significance in osteosarcoma. We demonstrated that TRAIP regulated the proliferation and invasion of osteosarcoma cells. In addition, we found that TRAIP promoted KANK1 polyubiquitination and subsequent degradation, downregulating IGFBP3 and activating the AKT pathway in osteosarcoma cells. These results support the critical role of the TRAIP/ KANK1/IGFBP3/AKT signaling axis in osteosarcoma progression and suggest that TRAIP may represent a promising therapeutic target for osteosarcoma. Cell Death and Disease (2021) 12:767 ; https://doi.org/10.1038/s41419-021-04057-0 INTRODUCTION mechanisms underlying osteosarcoma metastasis. We identified Mesenchymal stem cell-derived osteosarcoma is one of the most TRAIP as a differentially expressed gene (DEG) with prognostic and common primary malignancies in bones [1], and it is particularly diagnostic significance. We also found that TRAIP regulated the common in children and adolescents. With the recent progress in proliferation and invasion of osteosarcoma cells.
    [Show full text]
  • RING-Type E3 Ligases: Master Manipulators of E2 Ubiquitin-Conjugating Enzymes and Ubiquitination☆
    Biochimica et Biophysica Acta 1843 (2014) 47–60 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamcr Review RING-type E3 ligases: Master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination☆ Meredith B. Metzger a,1, Jonathan N. Pruneda b,1, Rachel E. Klevit b,⁎, Allan M. Weissman a,⁎⁎ a Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, 1050 Boyles Street, Frederick, MD 21702, USA b Department of Biochemistry, Box 357350, University of Washington, Seattle, WA 98195, USA article info abstract Article history: RING finger domain and RING finger-like ubiquitin ligases (E3s), such as U-box proteins, constitute the vast Received 5 March 2013 majority of known E3s. RING-type E3s function together with ubiquitin-conjugating enzymes (E2s) to medi- Received in revised form 23 May 2013 ate ubiquitination and are implicated in numerous cellular processes. In part because of their importance in Accepted 29 May 2013 human physiology and disease, these proteins and their cellular functions represent an intense area of study. Available online 6 June 2013 Here we review recent advances in RING-type E3 recognition of substrates, their cellular regulation, and their varied architecture. Additionally, recent structural insights into RING-type E3 function, with a focus on im- Keywords: RING finger portant interactions with E2s and ubiquitin, are reviewed. This article is part of a Special Issue entitled: U-box Ubiquitin–Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf. Ubiquitin ligase (E3) Published by Elsevier B.V. Ubiquitin-conjugating enzyme (E2) Protein degradation Catalysis 1.
    [Show full text]
  • The Extremely Conserved Amino Terminus of RAD6 Ubiquitin-Conju: Atlng Enzyme Is Essential for Amino-Endgrule-Dependent Protein Degradation
    Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press The extremely conserved amino terminus of RAD6 ubiquitin-conju: atlng enzyme is essential for amino-endgrule-dependent protein degradation John F. Watkins, Patrick Sung, 1 Satya Prakash, 1 and Louise Prakash Department of Biophysics, University of Rochester School of Medicine, Rochester, New York 14642 USA; ~Department of Biology, University of Rochester, Rochester, New York 14627 USA The RAD6 gene of Saccharomyces cererisiae encodes a ubiquitin-conjugating enzyme that is required for DNA repair, damage-induced mutagenesis, and sporulation. In addition, RAD6 mediates the multiubiquitination and degradation of amino-end rule protein substrates. The structure and function of RAD6 have been remarkably conserved during eukaryotic evolution. Here, we examine the role of the extremely conserved amino terminus, which has remained almost invariant among RAD6 homologs from yeast to human. We show that RAD6 is concentrated in the nucleus and that the amino-terminal deletion mutation, rad6al.9, does not alter the location of the protein. The amino-terminal domain, however, is essential for the multiubiquitination and degradation of amino-end rule substrates. In the rad6al_ 9 mutant, 13-galactosidase proteins bearing destabilizing amino-terminal residues become long lived, and purified rad6Al_9 protein is ineffective in ubiquitin-protein ligase (E3)-dependent protein degradation in the proteolytic system derived from rabbit reticulocytes. The amino terminus is required for physical interaction of RAD6 with the yeast UBRl-encoded E3 enzyme, as the rad6Al_9 protein is defective in this respect. The rad6al_9 mutant is defective in sporulation, shows reduced efficiency of DNA repair, but is proficient in UV mutagenesis.
    [Show full text]
  • Supplementary Material Table of Contents
    Supplementary M aterial Table of Contents 1 - Online S u pplementary Methods ………………………………………………...… . …2 1.1 Study population……………………………………………………………..2 1.2 Quality control and principal component analysis …………………………..2 1.3 Statistical analyses………………………………………… ………………...3 1.3.1 Disease - specific association testing ……………………………… ..3 1.3.2 Cross - phenotype meta - analysis …………………………………… .3 1.3.3 Model search ……………………………………………………… .4 1.3.4 Novelty of the variants …………………………………………… ..4 1.3.5 Functional Enrichment Analy sis ………………………………… ...4 1.3.6 Drug Target Enrichment Analysis ………………………………… 5 2 - Supplementary Figures………………………………………...………………… . …. 7 3 - Members of the Myositis Genetics Consortium (MYOGEN) ……………………. ..16 4 - Members of the Scleroderma Genetics Consortium ………………… ……………...17 5 - Supplementary References………………………………………………………… . .18 6 - Supplementary Tables………………………………………………………… . ……22 1 Online supplementary m ethods Study population This study was conducted using 12,132 affected subjects and 23 ,260 controls of European des cent population and all of them have been included in previously published GWAS as summarized in Table S1. [1 - 6] Briefly, a total of 3,255 SLE cases and 9,562 ancestry matched controls were included from six countrie s across Europe and North America (Spain, Germany, Netherlands, Italy, UK, and USA). All of the included patients were diagnosed based on the standard American College of Rheumatology (ACR) classification criteria. [7] Previously described GWAS data from 2,363 SSc cases and 5,181 ancestry
    [Show full text]
  • Chaperoning Proteins for Destruction: Diverse Roles of Hsp70 Chaperones and Their Co-Chaperones in Targeting Misfolded Proteins to the Proteasome
    Biomolecules 2014, 4, 704-724; doi:10.3390/biom4030704 OPEN ACCESS biomolecules ISSN 2218-273X www.mdpi.com/journal/biomolecules/ Review Chaperoning Proteins for Destruction: Diverse Roles of Hsp70 Chaperones and their Co-Chaperones in Targeting Misfolded Proteins to the Proteasome Ayala Shiber and Tommer Ravid * Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat-Ram, Jerusalem 91904, Israel; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +972-2-658-4349; Fax: +972-2-658-5449. Received: 28 March 2014; in revised form: 31 May 2014 / Accepted: 24 June 2014 / Published: 17 July 2014 Abstract: Molecular chaperones were originally discovered as heat shock-induced proteins that facilitate proper folding of proteins with non-native conformations. While the function of chaperones in protein folding has been well documented over the last four decades, more recent studies have shown that chaperones are also necessary for the clearance of terminally misfolded proteins by the Ub-proteasome system. In this capacity, chaperones protect misfolded degradation substrates from spontaneous aggregation, facilitate their recognition by the Ub ligation machinery and finally shuttle the ubiquitylated substrates to the proteasome. The physiological importance of these functions is manifested by inefficient proteasomal degradation and the accumulation of protein aggregates during ageing or in certain neurodegenerative diseases, when chaperone levels decline. In this review, we focus on the diverse roles of stress-induced chaperones in targeting misfolded proteins to the proteasome and the consequences of their compromised activity.
    [Show full text]
  • The Proteasomal Deubiquitinating Enzyme PSMD14 Regulates Macroautophagy by Controlling Golgi-To-ER Retrograde Transport
    Supplementary Materials The proteasomal deubiquitinating enzyme PSMD14 regulates macroautophagy by controlling Golgi-to-ER retrograde transport Bustamante HA., et al. Figure S1. siRNA sequences directed against human PSMD14 used for Validation Stage. Figure S2. Primer pairs sequences used for RT-qPCR. Figure S3. The PSMD14 DUB inhibitor CZM increases the Golgi apparatus area. Immunofluorescence microscopy analysis of the Golgi area in parental H4 cells treated for 4 h either with the vehicle (DMSO; Control) or CZM. The Golgi marker GM130 was used to determine the region of interest in each condition. Statistical significance was determined by Student's t-test. Bars represent the mean ± SEM (n =43 cells). ***P <0.001. Figure S4. CZM causes the accumulation of KDELR1-GFP at the Golgi apparatus. HeLa cells expressing KDELR1-GFP were either left untreated or treated with CZM for 30, 60 or 90 min. Cells were fixed and representative confocal images were acquired. Figure S5. Effect of CZM on proteasome activity. Parental H4 cells were treated either with the vehicle (DMSO; Control), CZM or MG132, for 90 min. Protein extracts were used to measure in vitro the Chymotrypsin-like peptidase activity of the proteasome. The enzymatic activity was quantified according to the cleavage of the fluorogenic substrate Suc-LLVY-AMC to AMC, and normalized to that of control cells. The statistical significance was determined by One-Way ANOVA, followed by Tukey’s test. Bars represent the mean ± SD of biological replicates (n=3). **P <0.01; n.s., not significant. Figure S6. Effect of CZM and MG132 on basal macroautophagy. (A) Immunofluorescence microscopy analysis of the subcellular localization of LC3 in parental H4 cells treated with either with the vehicle (DMSO; Control), CZM for 4 h or MG132 for 6 h.
    [Show full text]
  • Aggresomal Sequestration and STUB1-Mediated Ubiquitylation During Mammalian Proteaphagy of Inhibited Proteasomes
    Aggresomal sequestration and STUB1-mediated ubiquitylation during mammalian proteaphagy of inhibited proteasomes Won Hoon Choia,b, Yejin Yuna,b, Seoyoung Parka,c, Jun Hyoung Jeona,b, Jeeyoung Leea,b, Jung Hoon Leea,c, Su-A Yangd, Nak-Kyoon Kime, Chan Hoon Jungb, Yong Tae Kwonb, Dohyun Hanf, Sang Min Lime, and Min Jae Leea,b,c,1 aDepartment of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 03080 Seoul, Korea; bDepartment of Biomedical Sciences, Seoul National University Graduate School, 03080 Seoul, Korea; cNeuroscience Research Institute, Seoul National University College of Medicine, 03080 Seoul, Korea; dScience Division, Tomocube, 34109 Daejeon, Korea; eConvergence Research Center for Diagnosis, Korea Institute of Science and Technology, 02792 Seoul, Korea; and fProteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, 03080 Seoul, Korea Edited by Richard D. Vierstra, Washington University in St. Louis, St. Louis, MO, and approved July 1, 2020 (received for review November 18, 2019) The 26S proteasome, a self-compartmentalized protease complex, additional LC3-interacting region; the target cargoes can be plays a crucial role in protein quality control. Multiple levels of docked onto phosphatidylethanolamine-modified LC3 (LC3-II) regulatory systems modulate proteasomal activity for substrate on the expanding phagophore membrane, enveloped by an hydrolysis. However, the destruction mechanism of mammalian autophagosome, and eventually degraded in the autolysosomes. proteasomes is poorly understood. We found that inhibited pro- Notably, the enzymatic cascade attaching the lipid moiety at the teasomes are sequestered into the insoluble aggresome via C-terminal glycine of the cleaved LC3 protein in autophagy re- HDAC6- and dynein-mediated transport.
    [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]
  • Cascade Profiling of the Ubiquitin-Proteasome System in Cancer Anastasiia Rulina
    Cascade profiling of the ubiquitin-proteasome system in cancer Anastasiia Rulina To cite this version: Anastasiia Rulina. Cascade profiling of the ubiquitin-proteasome system in cancer. Agricultural sciences. Université Grenoble Alpes, 2015. English. NNT : 2015GREAV028. tel-01321321 HAL Id: tel-01321321 https://tel.archives-ouvertes.fr/tel-01321321 Submitted on 25 May 2016 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. THÈSE Pour obtenir le grade de DOCTEUR DE L’UNIVERSITÉ GRENOBLE ALPES Spécialité : Biodiversite du Developpement Oncogenese Arrêté ministériel : 7 août 2006 Présentée par Anastasiia Rulina Thèse dirigée par Maxim Balakirev préparée au sein du Laboratoire BIOMICS dans l'École Doctorale Chimie et Sciences du Vivant Profilage en cascade du système ubiquitine- protéasome dans le cancer Thèse soutenue publiquement le «17/12/2015», devant le jury composé de : M. Damien ARNOULT Docteur CR1, CNRS, Rapporteur M. Matthias NEES Professor Adjunct, University of Turku, Rapporteur M. Philippe SOUBEYRAN Docteur, INSERM, Membre Mme. Jadwiga CHROBOCZEK Directeur de recherche DR1, CNRS, Membre M. Xavier GIDROL Directeur de laboratoire, CEA, Président du jury M. Maxim BALAKIREV Docteur, CEA, Membre, Directeur de Thèse 2 Я посвящаю эту научную работу моей маме, Рулиной Людмиле Михайловне, с любовью и благодарностью.
    [Show full text]