DF2589-MUL1 Antibody

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Affinity Biosciences website:www.affbiotech.com order:[email protected] MUL1 Antibody Cat.#: DF2589 Concn.: 1mg/ml Mol.Wt.: 38 kDa Size: 50ul,100ul,200ul Source: Rabbit Clonality: Polyclonal Application: WB 1:500-1:2000, ELISA(peptide) 1:20000-1:40000 *The optimal dilutions should be determined by the end user. Reactivity: Human,Mouse,Rat Purification: The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific). Specificity: MUL1 Antibody detects endogenous levels of total MUL1. Immunogen: A synthesized peptide derived from human MUL1, corresponding to a region within the internal amino acids. Uniprot: Q969V5 Description: Exhibits weak E3 ubiquitin-protein ligase activity, but preferentially acts as a SUMO E3 ligase at physiological concentrations. Plays a role in the control of mitochondrial morphology. Promotes mitochondrial fragmentation and influences mitochondrial localization. Inhibits cell growth. When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. Storage Condition and Rabbit IgG in phosphate buffered saline, pH 7.4, 150mM Buffer: NaCl, 0.02% sodium azide and 50% glycerol. Western blot analysis of extracts from various samples, using MUL1 Antibody. Lane 1: Rat liver, blocked with antigen-specific peptides, Lane 2: Rat liver, Lane 3: Hela cells. 1 / 2 Affinity Biosciences website:www.affbiotech.com order:[email protected] Western blot analysis of MUL1 expression in A431 whole cell lysates ,The lane on the left was treated with the antigen- specific peptide. IMPORTANT: For western blot, incubate membrane with diluted primary Ab in 5% w/v milk , 1X TBS, 0.1% Tween®20 at 4°C with gentle shaking, overnight. For Research Use Only. Not for use in diagnostic and therapeutic procedures. Not for resale without express authorization. 2 / 2 Powered by TCPDF (www.tcpdf.org).

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MUL1 Polyclonal Antibody Catalog Number PA5-29550 Product Data Sheet
Lot Number: TE2564971L Website: thermofisher.com Customer Service (US): 1 800 955 6288 ext. 1 Technical Support (US): 1 800 955 6288 ext. 441 thermofisher.com/contactus MUL1 Polyclonal Antibody Catalog Number PA5-29550 Product Data Sheet Details Species Reactivity Size 100 µL Tested species reactivity Human Host / Isotype Rabbit IgG Tested Applications Dilution * Class Polyclonal Immunocytochemistry (ICC) 1:100-1:1000 Type Antibody Immunofluorescence (IF) 1:100-1:1000 Recombinant fragment Immunohistochemistry (Paraffin) Immunogen corresponding to a region within 1:100-1:1000 amino acids 1 and 352 of Human (IHC (P)) MUL1 Western Blot (WB) 1:500-1:3000 Conjugate Unconjugated * Suggested working dilutions are given as a guide only. It is recommended that the user titrate the product for use in their Form Liquid own experiment using appropriate negative and positive controls. Concentration 1.34mg/ml Purification Antigen affinity chromatography Storage Buffer PBS, pH 7, with 1% BSA, 20% glycerol Contains 0.025% Proclin 300 Storage Conditions -20° C, Avoid Freeze/Thaw Cycles Product Specific Information PA5-29550 targets MUL1 in IF and WB applications and shows reactivity with Human samples. The PA5-29550 immunogen is recombinant fragment corresponding to a region within amino acids 1 and 352 of Human MUL1. Background/Target Information E3 ubiquitin-protein ligase that plays a role in the control of mitochondrial morphology. Promotes mitochondrial fragmentation and influences mitochondrial localization. Inhibits cell growth. When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.
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Efficacy and Mechanistic Evaluation of Tic10, a Novel Antitumor Agent
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2012 Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent Joshua Edward Allen University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Oncology Commons Recommended Citation Allen, Joshua Edward, "Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent" (2012). Publicly Accessible Penn Dissertations. 488. https://repository.upenn.edu/edissertations/488 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/488 For more information, please contact [email protected]. Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent Abstract TNF-related apoptosis-inducing ligand (TRAIL; Apo2L) is an endogenous protein that selectively induces apoptosis in cancer cells and is a critical effector in the immune surveillance of cancer. Recombinant TRAIL and TRAIL-agonist antibodies are in clinical trials for the treatment of solid malignancies due to the cancer-specific cytotoxicity of TRAIL. Recombinant TRAIL has a short serum half-life and both recombinant TRAIL and TRAIL receptor agonist antibodies have a limited capacity to perfuse to tissue compartments such as the brain, limiting their efficacy in certain malignancies. To overcome such limitations, we searched for small molecules capable of inducing the TRAIL gene using a high throughput luciferase reporter gene assay. We selected TRAIL-inducing compound 10 (TIC10) for further study based on its induction of TRAIL at the cell surface and its promising therapeutic index. TIC10 is a potent, stable, and orally active antitumor agent that crosses the blood-brain barrier and transcriptionally induces TRAIL and TRAIL-mediated cell death in a p53-independent manner.
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The Contributions of Microglial Vps35 to Adult Hippocampal Neurogenesis and Neurodegenerative Disorders
THE CONTRIBUTIONS OF MICROGLIAL VPS35 TO ADULT HIPPOCAMPAL NEUROGENESIS AND NEURODEGENERATIVE DISORDERS By Joanna Ruth Erion Submitted to the Faculty of the Graduate School of Augusta University in partial fulfillment of the Requirements of the Degree of Doctor of Philosophy April 2017 COPYRIGHT© 2017 by Joanna Ruth Erion THE CONTRIBUTIONS OF MICROGLIAL VPS35 TO ADULT HIPPOCAMPAL NEUROGENESIS AND NEURODEGENERATIVE DISORDERS This thesis/dissertation is submitted by Joanna Ruth Erion and has been examined and approved by an appointed committee of the faculty of the Graduate School of Augusta University. The signatures which appear below verify the fact that all required changes have been incorporated and that the thesis/dissertation has received final approval with reference to content, form and accuracy of presentation. This thesis/dissertation is therefore in partial fulfillment of the requirements for the degree of Doctor of Philosophy). ___________________ __________________________________ Date Major Advisor __________________________________ Departmental Chairperson __________________________________ Dean, Graduate School ACKNOWLEDGEMENTS I will be forever grateful to my mentor, Dr. Wen-Cheng Xiong, for welcoming me into her laboratory and providing me with the honor and opportunity to work under her astute leadership. I have learned many valuable lessons under her guidance, all of which have enabled me to grow as both a student and a scientist. It was with her erudite guidance and suggestions that I was able to examine aspects of my investigations that I had yet to consider and ask questions that would not have otherwise occurred to me. I would also like to thank Dr. Lin Mei for contributing not only his laboratory and resources to my endeavors, but also his guidance and input into my investigations, providing me with additional avenues for directing my efforts.
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Protein Kinases and Parkinson's Disease
International Journal of Molecular Sciences Review Protein Kinases and Parkinson’s Disease Syed Jafar Mehdi 1, Hector Rosas-Hernandez 2, Elvis Cuevas 2, Susan M. Lantz 2, Steven W. Barger 1,3, Sumit Sarkar 2, Merle G. Paule 2, Syed F. Ali 2 and Syed Z. Imam 1,2,* 1 Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; [email protected] (S.J.M.); [email protected] (S.W.B.) 2 Division of Neurotoxicology, National Center for Toxicological Research/US Food and Drug Administration, Jefferson, AR 72079, USA; [email protected] (H.R.-H.); [email protected] (E.C.); [email protected] (S.M.L.); [email protected] (S.S.); [email protected] (M.G.P.); [email protected] (S.F.A.) 3 Geriatric Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA * Correspondence: [email protected]; Tel.: +1-870-543-7989; Fax: +1-870-543-7745 Academic Editor: Katalin Prokai-Tatrai Received: 30 May 2016; Accepted: 1 September 2016; Published: 20 September 2016 Abstract: Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensiﬁed the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease.
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Coupling of Terminal Differentiation Deficit with Neurodegenerative Pathology in Vps35-Deficient Pyramidal Neurons
Cell Death & Differentiation (2020) 27:2099–2116 https://doi.org/10.1038/s41418-019-0487-2 ARTICLE Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons 1 1,2,3 2,3 1,2 3 1,2 1,2 Fu-Lei Tang ● Lu Zhao ● Yang Zhao ● Dong Sun ● Xiao-Juan Zhu ● Lin Mei ● Wen-Cheng Xiong Received: 20 June 2019 / Revised: 13 December 2019 / Accepted: 17 December 2019 / Published online: 6 January 2020 © The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare 2020. This article is published with open access Abstract Vps35 (vacuolar protein sorting 35) is a key component of retromer that regulates transmembrane protein trafficking. Dysfunctional Vps35 is a risk factor for neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases. Vps35 is highly expressed in developing pyramidal neurons, and its physiological role in developing neurons remains to be explored. Here, we provide evidence that Vps35 in embryonic neurons is necessary for axonal and dendritic terminal differentiation. Loss of Vps35 in embryonic neurons results in not only terminal differentiation deficits, but also neurodegenerative pathology, such as cortical brain atrophy and reactive glial responses. The atrophy of neocortex appears to be in association with increases in neuronal death, autophagosome proteins (LC3-II and P62), and neurodegeneration associated proteins (TDP43 and ubiquitin-conjugated proteins). Further studies reveal an increase of retromer cargo protein, sortilin1 (Sort1), in lysosomes of Vps35-KO neurons, and lysosomal dysfunction. Suppression of Sort1 diminishes Vps35- KO-induced dendritic defects. Expression of lysosomal Sort1 recapitulates Vps35-KO-induced phenotypes.
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Mul1 Suppresses Nlrp3 Inflammasome Activation Through Ubiquitination And
bioRxiv preprint doi: https://doi.org/10.1101/830380; this version posted November 4, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Mul1 suppresses Nlrp3 inflammasome activation through ubiquitination and degradation of Asc June-Hyung Kim1, Yunjong Lee1, Gee Young Suh2, Yun-Song Lee1 1. Division of Pharmacology, Department of Molecular & Cellular Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea 2. Department of Critical Care Medicine in Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Running title: Mul1-mediated Asc ubiquitination Correspondence: Yun-Song Lee, M.D., Ph.D. Division of Pharmacology, Department of Molecular & Cellular Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea Tel: +82 31-299-6190 Fax: +82 31-299-6209 E-mail: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/830380; this version posted November 4, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Activation of the Nlrp3 inflammasome consisting of three major components, Nlrp3, Asc, and pro-caspase-1, results in the activation of caspase-1 and subsequent proteolytic cleavage of pro-IL-1β and pro-IL-18. To avoid excessive inflammatory response, the Nlrp3 inflammasome has to be precisely controlled.
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MUL1 (T-13): Sc-160072
SAN TA C RUZ BI OTEC HNOL OG Y, INC . MUL1 (T-13): sc-160072 BACKGROUND APPLICATIONS MUL1 (mitochondrial E3 ubiquitin protein ligase 1), also known as GIDE, MUL1 (T-13) is recommended for detection of MUL1 of mouse, rat and MAPL, MULAN or RNF218, is a 352 amino acid multi-pass mitochondrial human origin by Western Blotting (starting dilution 1:200, dilution range outer membrane protein that is widely expressed with highest levels in 1:100-1:1000), immunoprecipitation [1-2 µg per 100-500 µg of total protein heart, skeletal muscle, placenta, kidney and liver. Existing as a homooligo- (1 ml of cell lysate)], immunofluorescence (starting dilution 1:50, dilution mer, MUL1 contains one RING-type zinc finger, which is required for E3 lig - range 1:50-1:500) and solid phase ELISA (starting dilution 1:30, dilution ase activity. MUL1 acts as an E3 ubiquitin-protein ligase that participates in range 1:30-1:3000). the control of mitochondrial morphology, promotes mitochondrial fragmenta - MUL1 (T-13) is also recommended for detection of MUL1 in additional tion and influences mitochondrial localization. Overexpression of MUL1 acti - species, including canine, bovine and porcine. vates JNK (c Jun N terminal kinase) through Tak1 (transforming growth fac - Suitable for use as control antibody for MUL1 siRNA (h): sc-78840, MUL1 tor β-activated kinase 1) and induces caspase-dependent apoptosis. MUL1 is encoded by a gene located on human chromosome 1, which spans 260 siRNA (m): sc-149706, MUL1 shRNA Plasmid (h): sc-78840-SH, MUL1 shRNA million base pairs, contains over 3,000 genes, comprises nearly 8% of the Plasmid (m): sc-149706-SH, MUL1 shRNA (h) Lentiviral Particles: sc-78840-V human genome and houses a large number of disease-associated gene.
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VPS35, the Retromer Complex and Parkinson's Disease
Journal of Parkinson’s Disease 7 (2017) 219–233 219 DOI 10.3233/JPD-161020 IOS Press Review VPS35, the Retromer Complex and Parkinson’s Disease Erin T. Williamsa,b, Xi Chena and Darren J. Moorea,∗ aCenter for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA bVan Andel Institute Graduate School, Van Andel Research Institute, Grand Rapids, MI, USA Accepted 13 January 2017 Abstract. Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene encoding a core component of the retromer complex, have recently emerged as a new cause of late-onset, autosomal dominant familial Parkinson’s disease (PD). A single missense mutation, AspD620Asn (D620N), has so far been unambiguously identiﬁed to cause PD in multiple individuals and families worldwide. The exact molecular mechanism(s) by which VPS35 mutations induce progressive neurodegeneration in PD are not yet known. Understanding these mechanisms, as well as the perturbed cellular pathways downstream of mutant VPS35, is important for the development of appropriate therapeutic strategies. In this review, we focus on the current knowledge surrounding VPS35 and its role in PD. We provide a critical discussion of the emerging data regarding the mechanisms underlying mutant VPS35-mediated neurodegeneration gleaned from genetic cell and animal models and highlight recent advances that may provide insight into the interplay between VPS35 and several other PD-linked gene products (i.e. ␣-synuclein, LRRK2 and parkin) in PD. Present data support a role for perturbed VPS35 and retromer function in the pathogenesis of PD. Keywords: VPS35, retromer, Parkinson’s disease (PD), endosomal sorting, mitochondria, autophagy, lysosome, ␣-synuclein, LRRK2, parkin INTRODUCTION bradykinesia, resting tremor, rigidity and postural instability, owing to the relatively selective degener- Parkinson’s disease (PD), a common progressive ation of nigrostriatal pathway dopaminergic neurons neurodegenerative movement disorder, belongs to the [1, 2].
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Specificity in Ubiquitination Triggered by Virus Infection
International Journal of Molecular Sciences Review Specificity in Ubiquitination Triggered by Virus Infection Haidong Gu * and Behdokht Jan Fada Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-313-577-6402 Received: 7 May 2020; Accepted: 5 June 2020; Published: 8 June 2020 Abstract: Ubiquitination is a prominent posttranslational modification, in which the ubiquitin moiety is covalently attached to a target protein to influence protein stability, interaction partner and biological function. All seven lysine residues of ubiquitin, along with the N-terminal methionine, can each serve as a substrate for further ubiquitination, which effectuates a diverse combination of mono- or poly-ubiquitinated proteins with linear or branched ubiquitin chains. The intricately composed ubiquitin codes are then recognized by a large variety of ubiquitin binding domain (UBD)-containing proteins to participate in the regulation of various pathways to modulate the cell behavior. Viruses, as obligate parasites, involve many aspects of the cell pathways to overcome host defenses and subjugate cellular machineries. In the virus-host interactions, both the virus and the host tap into the rich source of versatile ubiquitination code in order to compete, combat, and co-evolve. Here, we review the recent literature to discuss the role of ubiquitin system as the infection progresses in virus life cycle and the importance of ubiquitin specificity in the regulation of virus-host relation. Keywords: ubiquitin code; virus infection; virus-host interaction 1. Introduction Ubiquitination is a reversible post-translational modification (PTM) that regulates protein functions in almost every aspect of a cell’s life.
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Parkinson's Disease–Associated VPS35 Mutant Reduces
Ma et al. Translational Neurodegeneration (2021) 10:19 https://doi.org/10.1186/s40035-021-00243-4 RESEARCH Open Access Parkinson’s disease–associated VPS35 mutant reduces mitochondrial membrane potential and impairs PINK1/Parkin- mediated mitophagy Kai Yu Ma1, Michiel R. Fokkens1, Fulvio Reggiori2, Muriel Mari2 and Dineke S. Verbeek1* Abstract Background: Mitochondrial dysfunction plays a prominent role in the pathogenesis of Parkinson’s disease (PD), and several genes linked to familial PD, including PINK1 (encoding PTEN-induced putative kinase 1 [PINK1]) and PARK2 (encoding the E3 ubiquitin ligase Parkin), are directly involved in processes such as mitophagy that maintain mitochondrial health. The dominant p.D620N variant of vacuolar protein sorting 35 ortholog (VPS35) gene is also associated with familial PD but has not been functionally connected to PINK1 and PARK2. Methods: To better mimic and study the patient situation, we used CRISPR-Cas9 to generate heterozygous human SH-SY5Y cells carrying the PD-associated D620N variant of VPS35. These cells were treated with a protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) to induce the PINK1/Parkin-mediated mitophagy, which was assessed using biochemical and microscopy approaches. Results: Mitochondria in the VPS35-D620N cells exhibited reduced mitochondrial membrane potential and appeared to already be damaged at steady state. As a result, the mitochondria of these cells were desensitized to the CCCP- induced collapse in mitochondrial potential, as they displayed altered fragmentation and were unable to accumulate PINK1 at their surface upon this insult. Consequently, Parkin recruitment to the cell surface was inhibited and initiation of the PINK1/Parkin-dependent mitophagy was impaired.
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Mitochondrial MUL1 E3 Ubiquitin Ligase Regulates Hypoxia Inducible Factor
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