24 results match your criteria ubx2

  • Page 1 of 1

Loss of ERAD bridging factor UBX2 modulates lipid metabolism and leads to ER stress-associated apoptosis during cadmium toxicity in Saccharomyces cerevisiae.

Curr Genet 2020 Oct 1;66(5):1003-1017. Epub 2020 Jul 1.

Biomembrane Lab, Department of Biochemistry, School of Life Science, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India.

The endoplasmic reticulum (ER) stress potentially activates the unfolded protein response (UPR) and ER-associated protein degradation (ERAD) as quality-control mechanisms. During ERAD process, the ERAD adaptor protein Ubx2 serves as a bridging factor and transports the misfolded proteins from the ER to the cytosol for subsequent ubiquitylation and proteasomal degradation. Cadmium (Cd) is a toxic metal that initiates ER stress and has an impact on lipid homeostasis and this study focuses on the synergistic impact of Cd exposure and ERAD (using ubx2∆ strain). Read More

View Article and Full-Text PDF
October 2020

A protein quality control pathway at the mitochondrial outer membrane.

Elife 2020 03 2;9. Epub 2020 Mar 2.

Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, United States.

Maintaining the essential functions of mitochondria requires mechanisms to recognize and remove misfolded proteins. However, quality control (QC) pathways for misfolded mitochondrial proteins remain poorly defined. Here, we establish temperature-sensitive (ts-) peripheral mitochondrial outer membrane (MOM) proteins as novel model QC substrates in . Read More

View Article and Full-Text PDF

A AAA ATPase Cdc48 with a cofactor Ubx2 facilitates ubiquitylation of a mitochondrial fusion-promoting factor Fzo1 for proteasomal degradation.

J Biochem 2020 Mar;167(3):279-286

Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.

Dynamic functionality of mitochondria is maintained by continual fusion and fission events. A mitochondrial outer membrane protein Fzo1 plays a pivotal role upon mitochondrial fusion by homo-oligomerization to tether fusing mitochondria. Fzo1 is tightly regulated by ubiquitylations and the ubiquitin-responsible AAA protein Cdc48. Read More

View Article and Full-Text PDF

Beyond ER: Regulating TOM-Complex-Mediated Import by Ubx2.

Trends Cell Biol 2019 09 26;29(9):687-689. Epub 2019 Jul 26.

McGill Parkinson Program, Neurodegenerative Diseases Group, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. Electronic address:

Despite the progress in understanding the molecular responses to mitochondrial damage, responses to aberrant accumulation of mitochondrial precursor proteins and mitochondrial import defects remain poorly understood. Recent work (Mårtensson et al., Nature, 2019) has unveiled a pathway similar to endoplasmic-reticulum-associated degradation (ERAD) in fine-tuning the fidelity of translocase of the outer mitochondrial membrane (TOM) complex-mediated mitochondrial import. Read More

View Article and Full-Text PDF
September 2019

Mitochondrial protein translocation-associated degradation.

Nature 2019 05 22;569(7758):679-683. Epub 2019 May 22.

Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Mitochondrial biogenesis and functions depend on the import of precursor proteins via the 'translocase of the outer membrane' (TOM complex). Defects in protein import lead to an accumulation of mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Read More

View Article and Full-Text PDF

Two Cdc48 cofactors Ubp3 and Ubx2 regulate mitochondrial morphology and protein turnover.

J Biochem 2018 Nov;164(5):349-358

Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto, Japan.

Mitochondria continuously undergo coordinated fusion and fission during vegetative growth to keep their homogeneity and to remove damaged components. A cytosolic AAA ATPase, Cdc48, is implicated in the mitochondrial fusion event and turnover of a fusion-responsible GTPase in the mitochondrial outer membrane, Fzo1, suggesting a possible linkage of mitochondrial fusion and Fzo1 turnover. Here, we identified two Cdc48 cofactor proteins, Ubp3 and Ubx2, involving mitochondria regulation. Read More

View Article and Full-Text PDF
November 2018

UBX domain-containing proteins are involved in lipid homeostasis and stress responses in Pichia pastoris.

Int J Biochem Cell Biol 2017 09 12;90:136-144. Epub 2017 Aug 12.

Ministry of Education Key Laboratory of Molecular Microbiology and Technology, Department of Microbiology, College of Life Science, Nankai University, Tianjin, 300071, PR China. Electronic address:

Ubiquitin regulatory X (UBX) domain-containing proteins constitute a family of proteins and are substrate adaptors of AAA ATPase Cdc48. UBX proteins can bind to the N-terminal region of Cdc48 to perform endoplasmic reticulum associated protein degradation (ERAD). In this study, we identified two UBX domain-containing proteins, Ubx1 and Ubx2, in Pichia pastoris and found that the two proteins could recover the growth defect of Saccharomyces cerevisiae in ubx2Δ. Read More

View Article and Full-Text PDF
September 2017

A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress.

Mol Cell 2013 Aug 25;51(4):519-30. Epub 2013 Jul 25.

Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.

Biological membranes are complex, and the mechanisms underlying their homeostasis are incompletely understood. Here, we present a quantitative genetic interaction map (E-MAP) focused on various aspects of lipid biology, including lipid metabolism, sorting, and trafficking. This E-MAP contains ∼250,000 negative and positive genetic interaction scores and identifies a molecular crosstalk of protein quality control pathways with lipid bilayer homeostasis. Read More

View Article and Full-Text PDF

Perturbations to the ubiquitin conjugate proteome in yeast δubx mutants identify Ubx2 as a regulator of membrane lipid composition.

Mol Cell Proteomics 2013 Oct 22;12(10):2791-803. Epub 2013 Jun 22.

Division of Biology.

Yeast Cdc48 (p97/VCP in human cells) is a hexameric AAA ATPase that is thought to use ATP hydrolysis to power the segregation of ubiquitin-conjugated proteins from tightly bound partners. Current models posit that Cdc48 is linked to its substrates through adaptor proteins, including a family of seven proteins (13 in human) that contain a Cdc48-binding UBX domain. However, few substrates for specific UBX proteins are known, and hence the generality of this hypothesis remains untested. Read More

View Article and Full-Text PDF
October 2013

The ubiquitin-like (UBX)-domain-containing protein Ubx2/Ubxd8 regulates lipid droplet homeostasis.

J Cell Sci 2012 Jun 27;125(Pt 12):2930-9. Epub 2012 Mar 27.

Institute of Plant and Microbial Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan.

Lipid droplets (LDs) are central organelles for maintaining lipid homeostasis. However, how cells control the size and number of LDs remains largely unknown. Herein, we report that Ubx2, a UBX-domain-containing protein involved in endoplasmic reticulum (ER)-associated degradation, is crucial for LD maintenance. Read More

View Article and Full-Text PDF

Dfm1 forms distinct complexes with Cdc48 and the ER ubiquitin ligases and is required for ERAD.

Traffic 2010 Oct;11(10):1363-9

Institut für Biochemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.

Proteins imported into the endoplasmic reticulum (ER) are scanned for their folding status. Those that do not reach their native conformation are degraded via the ubiquitin-proteasome system. This process is called ER-associated degradation (ERAD). Read More

View Article and Full-Text PDF
October 2010

Ubx4 modulates cdc48 activity and influences degradation of misfolded proteins of the endoplasmic reticulum.

J Biol Chem 2009 Jun 9;284(24):16082-16089. Epub 2009 Apr 9.

From the Institut für Biochemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany. Electronic address:

Misfolded proteins of the secretory pathway are recognized in the endoplasmic reticulum (ER), retrotranslocated into the cytoplasm, and degraded by the ubiquitin-proteasome system. Right after retrotranslocation and polyubiquitination, they are extracted from the cytosolic side of the ER membrane through a complex consisting of the AAA ATPase Cdc48 (p97 in mammals), Ufd1, and Npl4. This complex delivers misfolded proteins to the proteasome for final degradation. Read More

View Article and Full-Text PDF

The fission yeast SEL1 domain protein Cfh3p: a novel regulator of the glucan synthase Bgs1p whose function is more relevant under stress conditions.

J Biol Chem 2009 Apr 23;284(17):11070-9. Epub 2009 Feb 23.

Departamento de Microbiología y Genética/Instituto de Microbiología Bioquímica, Universidad de Salamanca/CSIC, 37007 Salamanca, Spain.

In Schizosaccharomyces pombe, Bgs1/Cps1p is a beta(1,3)-glucan synthase required for linear beta(1,3)-glucan synthesis and primary septum formation. Here, we have studied the regulation of Bgs1p by Cfh3/Chr4p, a member of a family of conserved adaptor proteins, which resembles the chitin synthase regulator Chs4p from Saccharomyces cerevisiae and Candida albicans. cfh3Delta cells showed a genetic interaction with cps1-191, and Cfh3p co-immunoprecipitated with Bgs1/Cps1p. Read More

View Article and Full-Text PDF

Original preparation of conjugates for antibody production against Amicoumacin-related anti-microbial agents.

Bioorg Med Chem 2008 Oct 7;16(20):9383-91. Epub 2008 Aug 7.

Université Bordeaux 1, EA 2975 UBX1-UBX2-ENITAB, F-33405 Talence Cedex, France.

Amicoumacins are natural products with potent anti-ulcerogenic and anti-bacterial activities, and have been isolated from different Bacillus genera. They belong to a family of 3,4-dihydroisocoumarin derivatives bearing hydroxylated amino acid side chains. The 3,4-dihydroisocoumarin moiety of Amicoumacins has been obtained in two steps from 2-methoxybenzoic acid by combining directed and benzylic metalation strategies. Read More

View Article and Full-Text PDF
October 2008

Synthesis of haptens and conjugates for ELISA of glycitein: development and validation of an immunological test.

J Agric Food Chem 2008 Aug 23;56(16):6809-17. Epub 2008 Jul 23.

Université de Bordeaux, EA 2975 UBX1-UBX2-ENITA de Bordeaux, F-33405, France.

Two carboxylic acid haptens of glycitein were synthesized, with a spacer arm at the C2 position. They differed in the length of the spacer arm, with the length of the spacer arms being three or four carbon atoms, and were named Delta3-glycitein and Delta4-glycitein haptens, respectively. The different haptens were coupled to bovine serum albumin (BSA), and the coupling efficiency was assessed by MALDI mass spectrometry. Read More

View Article and Full-Text PDF

Helicobacter pylori evolution: lineage- specific adaptations in homologs of eukaryotic Sel1-like genes.

PLoS Comput Biol 2007 Aug 19;3(8):e151. Epub 2007 Jun 19.

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.

Geographic partitioning is postulated to foster divergence of Helicobacter pylori populations as an adaptive response to local differences in predominant host physiology. H. pylori's ability to establish persistent infection despite host inflammatory responses likely involves active management of host defenses using bacterial proteins that may themselves be targets for adaptive evolution. Read More

View Article and Full-Text PDF

Sel1p/Ubx2p participates in a distinct Cdc48p-dependent endoplasmic reticulum-associated degradation pathway.

Traffic 2006 Sep;7(9):1213-23

Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.

The endoplasmic reticulum (ER) serves a critical role in the biogenesis of secretory proteins. Folding of nascent polypeptides occurs in the ER before anterograde transport through the secretory pathway, whereas terminally misfolded secretory proteins are recognized and eliminated by ER-associated degradation (ERAD). Here, we investigated the role of the ubiquitin regulatory X (UBX) domain-containing protein Sel1p in ER quality control and transport. Read More

View Article and Full-Text PDF
September 2006

Have you HRD? Understanding ERAD is DOAble!

Cell 2006 Jul;126(2):237-9

Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, Singapore 117604.

Numerous factors are involved in the eradication of misfolded proteins, yet how these factors achieve substrate specificity remains unclear. In this issue of Cell, Denic et al. (2006) and Carvalho et al. Read More

View Article and Full-Text PDF

Cdc48p is UBX-linked to ER ubiquitin ligases.

Karin Römisch

Trends Biochem Sci 2006 Jan 28;31(1):24-5. Epub 2005 Nov 28.

University of Cambridge, Cambridge Institute for Medical Research and Department of Clinical Biochemistry, Hills Road, Cambridge CB2 2XY, UK.

Proteasome-mediated turnover of misfolded secretory and transmembrane proteins at the cytoplasmic face of the endoplasmic reticulum (ER) membrane is dependent on a AAA-ATPase complex formed by the ubiquitin-selective chaperone Cdc48p in Saccharomyces cerevisiae and mammals by the Cdc48p homologue p97. Two new papers reveal that the Ubx2 protein physically links ER-membrane-integrated ubiquitin ligases to Cdc48p, and that it is essential for degradation of substrates that are ubiquitylated at the cytoplasmic face of the ER. Read More

View Article and Full-Text PDF
January 2006

Ubx2 links the Cdc48 complex to ER-associated protein degradation.

Nat Cell Biol 2005 Oct 18;7(10):993-8. Epub 2005 Sep 18.

Max-Delbrück Center for Molecular Medicine, Robert-Rössle Strasse 10, 13092 Berlin, Germany.

Endoplasmic reticulum (ER)-associated protein degradation requires the dislocation of selected substrates from the ER to the cytosol for proteolysis via the ubiquitin-proteasome system. The AAA ATPase Cdc48 (known as p97 or VCP in mammals) has a crucial, but poorly understood role in this transport step. Here, we show that Ubx2 (Sel1) mediates interaction of the Cdc48 complex with the ER membrane-bound ubiquitin ligases Hrd1 (Der3) and Doa10. Read More

View Article and Full-Text PDF
October 2005

Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their substrates to ensure efficient ER-associated protein degradation.

Nat Cell Biol 2005 Oct 18;7(10):999-1006. Epub 2005 Sep 18.

Max Planck Institute of Biochemistry, Department of Molecular Cell Biology, Am Klopferspitz 18, 82152 Martinsried, Germany.

Endoplasmic reticulum (ER)-associated protein degradation (ERAD) is a quality control system that removes misfolded proteins from the ER. ERAD substrates are channelled from the ER via a proteinacious pore to the cytosolic ubiquitin-proteasome system - a process involving dedicated ubiquitin ligases and the chaperone-like AAA ATPase Cdc48 (also known as p97). How the activities of these proteins are coupled remains unclear. Read More

View Article and Full-Text PDF
October 2005

Shp1 and Ubx2 are adaptors of Cdc48 involved in ubiquitin-dependent protein degradation.

EMBO Rep 2004 Aug 16;5(8):818-24. Epub 2004 Jul 16.

Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.

Known activities of the ubiquitin-selective AAA ATPase Cdc48 (p97) require one of the mutually exclusive cofactors Ufd1/Npl4 and Shp1 (p47). Whereas Ufd1/Npl4 recruits Cdc48 to ubiquitylated proteins destined for degradation by the 26S proteasome, the UBX domain protein p47 has so far been linked exclusively to nondegradative Cdc48 functions in membrane fusion processes. Here, we show that all seven UBX domain proteins of Saccharomyces cerevisiae bind to Cdc48, thus constituting an entire new family of Cdc48 cofactors. Read More

View Article and Full-Text PDF

The Ubx2 and Ubx3 cofactors direct Cdc48 activity to proteolytic and nonproteolytic ubiquitin-dependent processes.

Curr Biol 2004 May;14(9):824-8

Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, EH4 2XU Edinburgh, United Kingdom.

Valosin-containing protein, VCP/p97 or Cdc48, is a eukaryotic ATPase involved in membrane fusion, protein transport, and protein degradation. We describe two proteins, Ubx2 and Ubx3, which interact with Cdc48 in fission yeast. Ubx3 is the ortholog of p47/Shp1, a previously described Cdc48 cofactor involved in membrane fusion, whereas Ubx2 is a novel protein. Read More

View Article and Full-Text PDF

Expression of the beta3 tubulin gene (beta Tub60D) in the visceral mesoderm of Drosophila is dependent on a complex enhancer that binds Tinman and UBX.

Mol Gen Genet 1999 Dec;262(4-5):643-58

Fachbereich Biologie, Entwicklungsbiologie, Philipps-Universität Marburg, Germany.

The beta3 tubulin gene of Drosophila is expressed in the major mesodermal derivatives during their differentiation. The gene is subject to complex stage- and tissue-specific transcriptional control by upstream as well as downstream regions. Analysis of the vm1 enhancer, which is responsible for tissue-specific expression in the visceral mesoderm and is localized in the intron, revealed a complex modular arrangement of regulatory elements. Read More

View Article and Full-Text PDF
December 1999
  • Page 1 of 1