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Kerrie E McNally, Rebecca Faulkner, Florian Steinberg, Matthew Gallon, Rajesh Ghai, David Pim, Paul Langton, Neil Pearson, Chris M Danson, Heike Nägele, Lindsey L Morris, Amika Singla, Brittany L Overlee, Kate J Heesom, Richard Sessions, Lawrence Banks, Brett M Collins, Imre Berger, Daniel D Billadeau, Ezra Burstein, Peter J Cullen
Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer...
October 2017: Nature Cell Biology
Mario Riera Romo
The COMMD Protein Family is highly conserved among multicellular eukaryotic organisms and many orthologs of human COMMD genes have been found in different species of plants, invertebrates, lower vertebrates and mammals. COMMD1 is the best characterized member of the family and is conserved among vertebrates. This protein represents a pleiotropic factor involved in the regulation of many cellular and physiological processes that include copper and cholesterol homeostasis, ionic transport, oxidative stress, protein aggregation, protein trafficking, NF-κB-mediated transcription, hypoxia induced transcription, DNA damage response and oncogenesis...
May 20, 2017: Journal of Cellular Biochemistry
Natalia Loaiza, Federico Oldoni, Jan A Kuivenhoven
PURPOSE OF REVIEW: To highlight very recent studies identifying novel regulatory molecules and mechanisms in plasma lipid metabolism. RECENT FINDINGS: Two novel regulatory mechanisms of LDL receptor (LDLR) intracellular trafficking have been described. The "COMMD/CCDC22/CCDC93" and "Wiskott-Aldrich syndrome protein and SCAR homologue" complexes were found to be involved in LDLR endosomal sorting and recycling, whereas the GRP94 was shown to protect LDLR from early degradation within the hepatocyte secretory pathway...
June 2017: Current Opinion in Lipidology
Weihua Zhan, Wenjuan Wang, Tianyu Han, Caifeng Xie, Tingting Zhang, Mingxi Gan, Jian-Bin Wang
COMMD protein family is an evolutionarily conserved gene family implicated in a number of critical processes including inflammation, copper homeostasis, sodium balance, endosomal sorting and cancer. In an effort to profile the expression pattern of COMMD family in several non-small cell lung cancer (NSCLC) cell lines, we found that compared with that in human bronchial epithelial (HBE) cells, the mRNA expression levels of five COMMD genes including COMMD3, COMMD4, COMMD5, COMMD6 and COMMD8 were significantly down-regulated, whereas COMMD9 was up-regulated in NSCLC cell lines...
January 2017: Cellular Signalling
Paulina Bartuzi, Daniel D Billadeau, Robert Favier, Shunxing Rong, Daphne Dekker, Alina Fedoseienko, Hille Fieten, Melinde Wijers, Johannes H Levels, Nicolette Huijkman, Niels Kloosterhuis, Henk van der Molen, Gemma Brufau, Albert K Groen, Alison M Elliott, Jan Albert Kuivenhoven, Barbara Plecko, Gernot Grangl, Julie McGaughran, Jay D Horton, Ezra Burstein, Marten H Hofker, Bart van de Sluis
The low-density lipoprotein receptor (LDLR) plays a pivotal role in clearing atherogenic circulating low-density lipoprotein (LDL) cholesterol. Here we show that the COMMD/CCDC22/CCDC93 (CCC) and the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complexes are both crucial for endosomal sorting of LDLR and for its function. We find that patients with X-linked intellectual disability caused by mutations in CCDC22 are hypercholesterolaemic, and that COMMD1-deficient dogs and liver-specific Commd1 knockout mice have elevated plasma LDL cholesterol levels...
March 11, 2016: Nature Communications
Haiying Li, Yeon Koo, Xicheng Mao, Luis Sifuentes-Dominguez, Lindsey L Morris, Da Jia, Naoteru Miyata, Rebecca A Faulkner, Jan M van Deursen, Marc Vooijs, Daniel D Billadeau, Bart van de Sluis, Ondine Cleaver, Ezra Burstein
Notch family members are transmembrane receptors that mediate essential developmental programs. Upon ligand binding, a proteolytic event releases the intracellular domain of Notch, which translocates to the nucleus to regulate gene transcription. In addition, Notch trafficking across the endolysosomal system is critical in its regulation. In this study we report that Notch recycling to the cell surface is dependent on the COMMD-CCDC22-CCDC93 (CCC) complex, a recently identified regulator of endosomal trafficking...
November 9, 2015: Journal of Cell Biology
Elio Esposito, Gennaro Napolitano, Alessandra Pescatore, Giuseppe Calculli, Maria Rosaria Incoronato, Antonio Leonardi, Matilde Valeria Ursini
NEMO/IKKγ is the regulatory subunit of the IκB Kinase (IKK) complex, required for the activation of the NF-κB pathway, which is involved in a variety of key processes, including immunity, inflammation, differentiation, and cell survival. Termination of NF-κB activity on specific -κB responsive genes, which is crucial for the resolution of inflammatory responses, can be achieved by direct degradation of the chromatin-bound NF-κB subunit RelA/p65, a process mediated by a protein complex that contains Copper Metabolism Murr1 Domain 1 (COMMD1)...
January 2016: Journal of Cellular Physiology
Christine A Phillips-Krawczak, Amika Singla, Petro Starokadomskyy, Zhihui Deng, Douglas G Osborne, Haiying Li, Christopher J Dick, Timothy S Gomez, Megan Koenecke, Jin-San Zhang, Haiming Dai, Luis F Sifuentes-Dominguez, Linda N Geng, Scott H Kaufmann, Marco Y Hein, Mathew Wallis, Julie McGaughran, Jozef Gecz, Bart van de Sluis, Daniel D Billadeau, Ezra Burstein
COMMD1 deficiency results in defective copper homeostasis, but the mechanism for this has remained elusive. Here we report that COMMD1 is directly linked to early endosomes through its interaction with a protein complex containing CCDC22, CCDC93, and C16orf62. This COMMD/CCDC22/CCDC93 (CCC) complex interacts with the multisubunit WASH complex, an evolutionarily conserved system, which is required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer. Interactions between the WASH complex subunit FAM21, and the carboxyl-terminal ends of CCDC22 and CCDC93 are responsible for CCC complex recruitment to endosomes...
January 1, 2015: Molecular Biology of the Cell
Paulina Bartuzi, Marten H Hofker, Bart van de Sluis
NF-κB is an important regulator of immunity and inflammation, and its activation pathway has been studied extensively. The mechanisms that downregulate the activity of NF-κB have also received a lot of attention, particularly since its activity needs to be terminated to prevent chronic inflammation and subsequent tissue damage. The COMMD family has been identified as a new group of proteins involved in NF-κB termination. All ten COMMD members share the structurally conserved carboxy-terminal motif, the COMM domain, and are ubiquitously expressed...
December 2013: Biochimica et Biophysica Acta
Yong Feng Liu, Marianne Swart, Ying Ke, Kevin Ly, Fiona J McDonald
The epithelial sodium channel (ENaC) plays an important role in controlling Na⁺ homeostasis, extracellular fluid volume, and blood pressure. Copper metabolism Murr1 domain-containing protein 1 (COMMD1) interacts with ENaC and downregulates ENaC. COMMD1 belongs to the COMMD family consisting of COMMD1-10, and all COMMD family members share a C-terminal COMM domain. Here, we report that COMMD2-10 also interacts with ENaC, and COMMD3 and COMMD9 were selected for further study. Amiloride-sensitive current in mammalian epithelia expressing ENaC was significantly reduced by COMMD3 or COMMD9, and ENaC expression at the cell surface was significantly decreased in the presence of COMMD3 or COMMD9...
July 1, 2013: American Journal of Physiology. Renal Physiology
Hyun-E Yeom, Susan M Heidrich
PURPOSE/OBJECTIVES: To describe relationships among perceived barriers to symptom management and quality of life and to test the mediating role of perceived communication difficulties on the relationships between other perceived barriers to symptom management and quality of life in older adult breast cancer survivors. DESIGN: Cross-sectional descriptive-correlational design using baseline data from a randomized, controlled trial that tested the efficacy and durability of the individualized representational intervention in reducing symptom distress and improving quality of life in older adult breast cancer survivors...
May 1, 2013: Oncology Nursing Forum
Petro Starokadomskyy, Nathan Gluck, Haiying Li, Baozhi Chen, Mathew Wallis, Gabriel N Maine, Xicheng Mao, Iram W Zaidi, Marco Y Hein, Fiona J McDonald, Steffen Lenzner, Agnes Zecha, Hans-Hilger Ropers, Andreas W Kuss, Julie McGaughran, Jozef Gecz, Ezra Burstein
NF-κB is a master regulator of inflammation and has been implicated in the pathogenesis of immune disorders and cancer. Its regulation involves a variety of steps, including the controlled degradation of inhibitory IκB proteins. In addition, the inactivation of DNA-bound NF-κB is essential for its regulation. This step requires a factor known as copper metabolism Murr1 domain-containing 1 (COMMD1), the prototype member of a conserved gene family. While COMMD proteins have been linked to the ubiquitination pathway, little else is known about other family members...
May 2013: Journal of Clinical Investigation
Ping Jin, Yingqiu Gao, Liming Chen, Fei Ma
The recently discovered COMM domain-containing (COMMD) protein family has ten members (COMMD1-10). A COMMD protein contains a carboxyl-terminal COMM (copper metabolism gene MURR1) domain which provides an interface for protein-protein interactions. However, no COMMD4 gene has been identified in amphioxus. In this study, we report the identification and characterization of a COMMD4 gene from the amphioxus (designated as AmphiCOMMD4). First, we cloned the full length of AmphiCOMMD4 gene and found that the deduced amino acid sequence of AmphiCOMMD4 has 55...
December 17, 2012: Immunology Letters
Muriel Bost, Guénaelle Piguet-Lacroix, François Parant, C M R Wilson
ATP7B mutations result in Cu storage in the liver and brain in Wilson disease (WD). Atox1 and COMMD1 were found to interact with ATP7B and involved in copper transport in the hepatocyte. To understand the molecular etiology of WD, we analyzed ATP7B, Atox1 and COMMD1 genes. Direct sequencing of (i) ATP7B gene was performed in 112 WD patients to identify the spectrum of disease-causing mutations in the French population, (ii) Atox1 gene was performed to study the known polymorphism 5'UTR-99T>C in 78 WD patients with two ATP7B mutations and (iii) COMMD1 gene was performed to detect the nucleotide change c...
June 2012: Journal of Trace Elements in Medicine and Biology
Zacharati Gkiafi, George Panayotou
Epstein-Barr virus (EBV) infection is a major health problem associated with a variety of diseases, including Burkitt's lymphoma. EBV promotes its effects through the activation of multiple signaling pathways, with NF-κB mediated transcription being a major target. We have undertaken a comparative proteomic approach using 2D-electrophoresis and mass spectrometry to identify EBV-regulated proteins in the BL41 Burkitt's lymphoma cell line. Many of the proteins differentially regulated were previously known mediators of EBV action...
July 1, 2011: Journal of Proteome Research
Bart van de Sluis, Xicheng Mao, Yali Zhai, Arjan J Groot, Jeroen F Vermeulen, Elsken van der Wall, Paul J van Diest, Marten H Hofker, Cisca Wijmenga, Leo W Klomp, Kathleen R Cho, Eric R Fearon, Marc Vooijs, Ezra Burstein
The gene encoding COMM domain-containing 1 (COMMD1) is a prototypical member of the COMMD gene family that has been shown to inhibit both NF-kappaB- and HIF-mediated gene expression. NF-kappaB and HIF are transcription factors that have been shown to play a role in promoting tumor growth, survival, and invasion. In this study, we demonstrate that COMMD1 expression is frequently suppressed in human cancer and that decreased COMMD1 expression correlates with a more invasive tumor phenotype. We found that direct repression of COMMD1 in human cell lines led to increased tumor invasion in a chick xenograft model, while increased COMMD1 expression in mouse melanoma cells led to decreased lung metastasis in a mouse model...
June 2010: Journal of Clinical Investigation
Jason L Burkhead, Clinton T Morgan, Ujwal Shinde, Gabrielle Haddock, Svetlana Lutsenko
Copper metabolism Murr1 domain 1 (COMMD1) is a 21-kDa protein involved in copper export from the liver, NF-kappaB signaling, HIV infection, and sodium transport. The precise function of COMMD and the mechanism through which COMMD1 performs its multiple roles are not understood. Recombinant COMMD1 is a soluble protein, yet in cells COMMD1 is largely seen as targeted to cellular membranes. Using co-localization with organelle markers and cell fractionation, we determined that COMMD1 is located in the vesicles of the endocytic pathway, whereas little COMMD1 is detected in either the trans-Golgi network or lysosomes...
January 2, 2009: Journal of Biological Chemistry
Gabriel N Maine, Xicheng Mao, Patricia A Muller, Christine M Komarck, Leo W J Klomp, Ezra Burstein
COMMD {COMM [copper metabolism Murr1 (mouse U2af1-rs1 region 1)] domain-containing} proteins participate in several cellular processes, ranging from NF-kappaB (nuclear factor kappaB) regulation, copper homoeostasis, sodium transport and adaptation to hypoxia. The best-studied member of this family is COMMD1, but relatively little is known about its regulation, except that XIAP [X-linked IAP (inhibitor of apoptosis)] functions as its ubiquitin ligase. In the present study, we identified that the COMM domain of COMMD1 is required for its interaction with XIAP, and other COMMD proteins can similarly interact with IAPs...
January 15, 2009: Biochemical Journal
G N Maine, E Burstein
COMM Domain-containing or COMMD proteins are a recently discovered group of factors defined by the presence of a unique motif in their extreme carboxy termini (Copper metabolism MURR1, or COMM domain). This protein family is comprised of ten members which are widely conserved throughout evolution and share certain functional properties. At the present time, a number of seemingly discrete functions have been ascribed to these factors. These include the regulation of such events as the activity of the transcription factor NF-kappaB, copper homeostasis, the function of the epithelial sodium channel, and cell proliferation...
August 2007: Cellular and Molecular Life Sciences: CMLS
Bart van de Sluis, Patricia Muller, Karen Duran, Amy Chen, Arjan J Groot, Leo W Klomp, Paul P Liu, Cisca Wijmenga
COMMD1 (previously known as MURR1) belongs to a novel family of proteins termed the copper metabolism gene MURR1 domain (COMMD) family. The 10 COMMD family members are well conserved between vertebrates, but the functions of most of the COMMD proteins are unknown. We recently established that COMMD1 is associated with the hepatic copper overload disorder copper toxicosis in Bedlington terriers. Recent in vitro studies indicate that COMMD1 has multiple functions, including sodium transport and NF-kappaB signaling...
June 2007: Molecular and Cellular Biology
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