DF2589-MUL1 Antibody

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Affinity Biosciences

website:www.affbiotech.com order:[email protected]

MUL1 Antibody

Cat.#: DF2589 Size: 50ul,100ul,200ul
Concn.: 1mg/ml Source: Rabbit
Mol.Wt.: 38 kDa 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 Buffer:
Rabbit IgG in phosphate buffered saline, pH 7.4, 150mM 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.

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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 antigenspecific 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.

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MUL1 Polyclonal Antibody Catalog Number PA5-29550 Product Data Sheet

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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.
The Contributions of Microglial Vps35 to Adult Hippocampal Neurogenesis and Neurodegenerative Disorders

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Protein Kinases and Parkinson's Disease

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Coupling of Terminal Differentiation Deficit with Neurodegenerative Pathology in Vps35-Deficient Pyramidal Neurons

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Positive Regulation of Pkb/Akt Kinase Activity by The

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Mul1 Suppresses Nlrp3 Inflammasome Activation Through Ubiquitination And

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MUL1 (T-13): Sc-160072

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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].
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.
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.
Mitochondrial MUL1 E3 Ubiquitin Ligase Regulates Hypoxia Inducible Factor

www.nature.com/scientificreports OPEN Mitochondrial MUL1 E3 ubiquitin ligase regulates Hypoxia Inducible Factor (HIF-1α) and metabolic reprogramming by modulating the UBXN7 cofactor protein Lucia Cilenti1,3, Jacopo Di Gregorio1,3, Camilla T. Ambivero1, Thomas Andl1, Ronglih Liao2 & Antonis S. Zervos1* MUL1 is a multifunctional E3 ubiquitin ligase anchored in the outer mitochondrial membrane with its RING fnger domain facing the cytoplasm. MUL1 participates in various biological pathways involved in apoptosis, mitochondrial dynamics, and innate immune response. The unique topology of MUL1 enables it to “sense” mitochondrial stress in the intermembrane mitochondrial space and convey these signals through the ubiquitination of specifc cytoplasmic substrates. We have identifed UBXN7, the cofactor protein of the CRL2VHL ligase complex, as a specifc substrate of MUL1 ligase. CRL2VHL ligase complex regulates HIF-1α protein levels under aerobic (normoxia) or anaerobic (hypoxia) conditions. Inactivation of MUL1 ligase leads to accumulation of UBXN7, with concomitant increase in HIF-1α protein levels, reduction in oxidative phosphorylation, and increased glycolysis. We describe a novel pathway that originates in the mitochondria and operates upstream of the CRL2VHL ligase complex. Furthermore, we delineate the mechanism by which the mitochondria, through MUL1 ligase, can inhibit the CRL2VHL complex leading to high HIF-1α protein levels and a metabolic shift to glycolysis under normoxic conditions. Eukaryotic cells are dependent on oxygen levels as well as the presence of functional mitochondria in order to efciently generate ATP through oxidative phosphorylation (OXPHOS). Cells respond quickly to changes in oxy- gen levels by activating several signaling pathways that provide metabolic and adaptive mechanisms to the new environment.