keyword
MENU ▼
Read by QxMD icon Read
search

IRhom2

keyword
https://www.readbyqxmd.com/read/28815577/emerging-roles-of-rhomboid-like-pseudoproteases-in-inflammatory-and-innate-immune-responses
#1
REVIEW
Wei-Wei Luo, Hong-Bing Shu
Rhomboid-like pseudoproteases are a conserved superfamily of proteins related to rhomboid intramembrane serine proteases that lack key catalytic residues. iRhom2, a member of the rhomboid-like pseudoprotease superfamily, has been reported to regulate the maturation and trafficking of ADAM17, and be associated with inflammatory arthritis. Recent studies demonstrate that iRhom2 is also involved in innate immunity by regulating the trafficking and stability of MITA (also called STING), which is a central adaptor in innate antiviral signalling pathways...
August 17, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28703301/the-xenoestrogens-biphenol-a-and-nonylphenol-differentially-regulate-metalloprotease-mediated-shedding-of-egfr-ligands
#2
Paulina Urriola-Muñoz, Xue Li, Thorsten Maretzky, David R McIlwain, Tak W Mak, Juan G Reyes, Carl P Blobel, Ricardo D Moreno
The xenoestrogens Bisphenol-A (BPA) and Nonylphenol (NP) are endocrine disruptors used in the plastic polymer industry to manufacture different products for human use. Previous studies have suggested a role of these compounds in the shedding of signaling molecules, such as tumor necrosis factor α (TNF- α). The aim of this work was to evaluate the effect of BPA and NP on the sheddase ADAM17 and its newly discovered regulators iRhom1 and iRhom2 in the release of EGFR-ligands. We report that BPA and NP can stimulate the release of the ADAM17-substrates HB-EGF and TGF- α...
July 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28432785/phosphorylation-of-irhom2-at-the-plasma-membrane-controls-mammalian-tace-dependent-inflammatory-and-growth-factor-signalling
#3
Adam Graham Grieve, Hongmei Xu, Ulrike Künzel, Paul Bambrough, Boris Sieber, Matthew Freeman
Proteolytic cleavage and release from the cell surface of membrane-tethered ligands is an important mechanism of regulating intercellular signalling. TACE is a major shedding protease, responsible for the liberation of the inflammatory cytokine TNFα and ligands of the epidermal growth factor receptor. iRhoms, catalytically inactive members of the rhomboid-like superfamily, have been shown to control the ER-to-Golgi transport and maturation of TACE. Here, we reveal that iRhom2 remains associated with TACE throughout the secretory pathway, and is stabilised at the cell surface by this interaction...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28132838/human-cytomegalovirus-tegument-protein-ul82-inhibits-sting-mediated-signaling-to-evade-antiviral-immunity
#4
Yu-Zhi Fu, Shan Su, Yi-Qun Gao, Pei-Pei Wang, Zhe-Fu Huang, Ming-Ming Hu, Wei-Wei Luo, Shu Li, Min-Hua Luo, Yan-Yi Wang, Hong-Bing Shu
Recognition of human cytomegalovirus (HCMV) DNA by the cytosolic sensor cGAS initiates STING-dependent innate antiviral responses. HCMV can antagonize host immune responses to promote latency infection. However, it is unknown whether and how HCMV targets the cGAS-STING axis for immune evasion. Here we identified the HCMV tegument protein UL82 as a negative regulator of STING-dependent antiviral responses. UL82 interacted with STING and impaired STING-mediated signaling via two mechanisms. UL82 inhibited the translocation of STING from the ER to perinuclear microsomes by disrupting the STING-iRhom2-TRAPβ translocation complex...
February 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28128203/rhomboid-family-member-2-regulates-cytoskeletal-stress-associated-keratin-16
#5
Thiviyani Maruthappu, Anissa Chikh, Benjamin Fell, Paul J Delaney, Matthew A Brooke, Clemence Levet, Angela Moncada-Pazos, Akemi Ishida-Yamamoto, Diana Blaydon, Ahmad Waseem, Irene M Leigh, Matthew Freeman, David P Kelsell
Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2(-/-) mice compared with irhom2(+/+)mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28104813/structural-modeling-defines-transmembrane-residues-in-adam17-that-are-crucial-for-rhbdf2-adam17-dependent-proteolysis
#6
Xue Li, Thorsten Maretzky, Jose Manuel Perez-Aguilar, Sébastien Monette, Gisela Weskamp, Sylvain Le Gall, Bruce Beutler, Harel Weinstein, Carl P Blobel
A disintegrin and metalloproteinase 17 (ADAM17) controls the release of the pro-inflammatory cytokine tumor necrosis factor α (TNFα, also known as TNF) and is crucial for protecting the skin and intestinal barrier by proteolytic activation of epidermal growth factor receptor (EGFR) ligands. The seven-membrane-spanning protein called inactive rhomboid 2 (Rhbdf2; also known as iRhom2) is required for ADAM17-dependent TNFα shedding and crosstalk with the EGFR, and a point mutation (known as sinecure, sin) in the first transmembrane domain (TMD) of Rhbdf2 (Rhbdf2(sin)) blocks TNFα shedding, yet little is known about the underlying mechanism...
March 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28033581/irhom2-is-involved-in-lipopolysaccharide-induced-cardiac-injury-in-vivo-and-in-vitro-through-regulating-inflammation-response
#7
Xue-Li Lu, Cui-Hua Zhao, Han Zhang, Xin-Liang Yao
Heart is a complex assembly of many cell types constituting of myocardium, endocardium and epicardium that intensively communicate to each other in order to maintain the proper cardiac function. Previous research has demonstrated that lipopolysaccharide (LPS) can induce myocardial dysfunction. iRhom2 is encoded by the gene Rhbdf2, regulating inflammation via tumor necrosis factor-α (TNF-α). In this study, we attempted to investigate the role of iRhom2 in LPS-induced cardiac injury and clarify the potential mechanism...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27601030/irhom2-regulates-csf1r-cell-surface-expression-and-non-steady-state-myelopoiesis-in-mice
#8
Xiaoping Qing, Lindsay Rogers, Arthur Mortha, Yonit Lavin, Patricia Redecha, Priya D Issuree, Thorsten Maretzky, Miriam Merad, David McIlwain, Tak W Mak, Christopher M Overall, Carl P Blobel, Jane E Salmon
CSF1R (colony stimulating factor 1 receptor) is the main receptor for CSF1 and has crucial roles in regulating myelopoeisis. CSF1R can be proteolytically released from the cell surface by ADAM17 (A disintegrin and metalloprotease 17). Here, we identified CSF1R as a major substrate of ADAM17 in an unbiased degradomics screen. We explored the impact of CSF1R shedding by ADAM17 and its upstream regulator, inactive rhomboid protein 2 (iRhom2, gene name Rhbdf2), on homeostatic development of mouse myeloid cells...
December 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27599715/stimulated-release-and-functional-activity-of-surface-expressed-metalloproteinase-adam17-in-exosomes
#9
Esther Groth, Jessica Pruessmeyer, Aaron Babendreyer, Julian Schumacher, Tobias Pasqualon, Daniela Dreymueller, Shigeki Higashiyama, Inken Lorenzen, Joachim Grötzinger, Didier Cataldo, Andreas Ludwig
By mediating proteolytic shedding on the cell surface the disintegrin and metalloproteinases ADAM10 and ADAM17 function as critical regulators of growth factors, cytokines and adhesion molecules. We here report that stimulation of lung epithelial A549 tumor cells with phorbol-12-myristate-13-acetate (PMA) leads to the downregulation of the surface expressed mature form of ADAM17 without affecting ADAM10 expression. This reduction could not be sufficiently explained by metalloproteinase-mediated degradation, dynamin-mediated internalization or microdomain redistribution of ADAM17...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27428826/irhom2-is-essential-for-innate-immunity-to-dna-viruses-by-mediating-trafficking-and-stability-of-the-adaptor-sting
#10
Wei-Wei Luo, Shu Li, Chen Li, Huan Lian, Qing Yang, Bo Zhong, Hong-Bing Shu
STING is a central adaptor in the innate immune response to DNA viruses. However, the manner in which STING activity is regulated remains unclear. We identified iRhom2 ('inactive rhomboid protein 2') as a positive regulator of DNA-virus-triggered induction of type I interferons. iRhom2 deficiency markedly impaired DNA-virus- and intracellular-DNA-induced signaling in cells, and iRhom2-deficient mice were more susceptible to lethal herpes simplex virus type 1 (HSV-1) infection. iRhom2 was constitutively associated with STING and acted in two distinct processes to regulate STING activity...
September 2016: Nature Immunology
https://www.readbyqxmd.com/read/27393687/irhom2-uncv-mutation-blocks-bulge-stem-cells-assuming-the-fate-of-hair-follicle
#11
Leilei Yang, Wenlong Li, Bing Liu, Shaoxia Wang, Lin Zeng, Cuiping Zhang, Yang Li
iRhom2 is necessary for maturation of TNFα-converting enzyme, which is required for the release of tumor necrosis factor. In the previous study, we found that the iRhom2 (Uncv) mutation in N-terminal cytoplasmic domain-encoding region (iRhom2 (Uncv) ) leads to aberrant hair shaft and inner root sheath differentiation, thus results in a hairless phenotype in homozygous iRhom2 (Uncv/Uncv) BALB/c mice. In this study, we found iRhom2 mutation decreased hair matrix proliferation, however, iRhom2 (Uncv/Uncv) mice displayed hyperproliferation and hyperkeratosis in the interfollicular epidermis along with hypertrophy in the sebaceous glands...
September 2016: Archives of Dermatological Research
https://www.readbyqxmd.com/read/27330189/met-signaling-in-keratinocytes-activates-egfr-and-initiates-squamous-carcinogenesis
#12
Christophe Cataisson, Aleksandra M Michalowski, Kelly Shibuya, Andrew Ryscavage, Mary Klosterman, Lisa Wright, Wendy Dubois, Fan Liu, Anne Zhuang, Kameron B Rodrigues, Shelley Hoover, Jennifer Dwyer, Mark R Simpson, Glenn Merlino, Stuart H Yuspa
The receptor tyrosine kinase MET is abundant in many human squamous cell carcinomas (SCCs), but its functional significance in tumorigenesis is not clear. We found that the incidence of carcinogen-induced skin squamous tumors was substantially increased in transgenic MT-HGF (mouse metallothionein-hepatocyte growth factor) mice, which have increased abundance of the MET ligand HGF. Squamous tumors also erupted spontaneously on the skin of MT-HGF mice that were promoted by wounding or the application of 12-O-tetradecanoylphorbol 13-acetate, an activator of protein kinase C...
2016: Science Signaling
https://www.readbyqxmd.com/read/27256961/regulation-of-a-disintegrin-and-metalloproteinase-adam-family-sheddases-adam10-and-adam17-the-emerging-role-of-tetraspanins-and-rhomboids
#13
Alexandra L Matthews, Peter J Noy, Jasmeet S Reyat, Michael G Tomlinson
A disintegrin and metalloprotease (ADAM) 10 and ADAM17 are ubiquitous transmembrane "molecular scissors" which proteolytically cleave, or shed, the extracellular regions of other transmembrane proteins. ADAM10 is essential for development because it cleaves Notch proteins to induce Notch signaling and regulate cell fate decisions. ADAM17 is regarded as a first line of defense against injury and infection, by releasing tumor necrosis factor α (TNFα) to promote inflammation and epidermal growth factor (EGF) receptor ligands to maintain epidermal barrier function...
June 2017: Platelets
https://www.readbyqxmd.com/read/27076598/endogenous-transmembrane-tnf-alpha-protects-against-premature-senescence-in-endothelial-colony-forming-cells
#14
Linden A Green, Victor Njoku, Julie Mund, Jaime Case, Mervin Yoder, Michael P Murphy, Matthias Clauss
RATIONALE: Transmembrane tumor necrosis factor-α (tmTNF-α) is the prime ligand for TNF receptor 2, which has been shown to mediate angiogenic and blood vessel repair activities in mice. We have previously reported that the angiogenic potential of highly proliferative endothelial colony-forming cells (ECFCs) can be explained by the absence of senescent cells, which in mature endothelial cells occupy >30% of the population, and that exposure to a chronic inflammatory environment induced premature, telomere-independent senescence in ECFCs...
May 13, 2016: Circulation Research
https://www.readbyqxmd.com/read/26869525/irhoms-its-functions-and-essential-roles
#15
Min-Young Lee, Ki-Hoan Nam, Kyung-Chul Choi
In Drosophila, rhomboid proteases are active cardinal regulators of epidermal growth factor receptor (EGFR) signaling pathway. iRhom1 and iRhom2, which are inactive homologs of rhomboid intramembrane serine proteases, are lacking essential catalytic residues. These are necessary for maturation and traffickingof tumor necrosis factor-alpha (TNF-α) converting enzyme (TACE) from endoplasmic reticulum (ER) to plasma membrane through Golgi, and associated with the fates of various ligands for EGFR. Recent studies have clarifiedthat the activation or downregulation of EGFR signaling pathways by alteration of iRhoms are connected to several human diseases including tylosis with esophageal cancer (TOC) which is the autosomal dominant syndrom, breast cancer, and Alzheimer's disease...
March 1, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/26603928/3d-structure-generation-molecular-dynamics-and-docking-studies-of-irhom2-protein-involved-in-cancer-rheumatoid-arthritis
#16
Utkarsh Raj, Himansu Kumar, Pritish Kumar Varadwaj
A short-lived membrane protein IRHOM2 pedals a cascade of events by regulating Epidermal Growth Factor Receptor (EGFR) signalling in parallel with metalloproteases which results their involvement in cancer as well as in rheumatoid arthritis. Therefore, IRHOM2 is a potential therapeutic drug target for these diseases, but its 3D-structure has not been reported yet. In this study, the three-dimensional structure of the IRHOM2 protein was generated using I-TASSER (Iterative Threading Assembly Refinement) server...
2015: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/26535007/deletions-in-the-cytoplasmic-domain-of-irhom1-and-irhom2-promote-shedding-of-the-tnf-receptor-by-the-protease-adam17
#17
Sathish K Maney, David R McIlwain, Robin Polz, Aleksandra A Pandyra, Balamurugan Sundaram, Dorit Wolff, Kazuhito Ohishi, Thorsten Maretzky, Matthew A Brooke, Astrid Evers, Ananda A Jaguva Vasudevan, Nima Aghaeepour, Jürgen Scheller, Carsten Münk, Dieter Häussinger, Tak W Mak, Garry P Nolan, David P Kelsell, Carl P Blobel, Karl S Lang, Philipp A Lang
The protease ADAM17 (a disintegrin and metalloproteinase 17) catalyzes the shedding of various transmembrane proteins from the surface of cells, including tumor necrosis factor (TNF) and its receptors. Liberation of TNF receptors (TNFRs) from cell surfaces can dampen the cellular response to TNF, a cytokine that is critical in the innate immune response and promotes programmed cell death but can also promote sepsis. Catalytically inactive members of the rhomboid family of proteases, iRhom1 and iRhom2, mediate the intracellular transport and maturation of ADAM17...
November 3, 2015: Science Signaling
https://www.readbyqxmd.com/read/25918388/irhoms-1-and-2-are-essential-upstream-regulators-of-adam17-dependent-egfr-signaling
#18
Xue Li, Thorsten Maretzky, Gisela Weskamp, Sébastien Monette, Xiaoping Qing, Priya Darshinee A Issuree, Howard C Crawford, David R McIlwain, Tak W Mak, Jane E Salmon, Carl P Blobel
The metalloproteinase ADAM17 (a disintegrin and metalloprotease 17) controls EGF receptor (EGFR) signaling by liberating EGFR ligands from their membrane anchor. Consequently, a patient lacking ADAM17 has skin and intestinal barrier defects that are likely caused by lack of EGFR signaling, and Adam17(-/-) mice die perinatally with open eyes, like Egfr(-/-) mice. A hallmark feature of ADAM17-dependent EGFR ligand shedding is that it can be rapidly and posttranslationally activated in a manner that requires its transmembrane domain but not its cytoplasmic domain...
May 12, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25546423/irhom2-mutation-leads-to-aberrant-hair-follicle-differentiation-in-mice
#19
Yang Leilei, Liu Bing, Li Yang, Wang Shaoxia, Xu Yuan, Wang Dongping, Ye Huahu, Shang Shichen, Zhang Guangzhou, Peng Ruiyun, Zeng Lin, Li Wenlong
iRhom1 and iRhom2 are inactive homologues of rhomboid intramembrane serine proteases lacking essential catalytic residues, which are necessary for the maturation of TNFα-converting enzyme (TACE). In addition, iRhoms regulate epidermal growth factor family secretion. The functional significance of iRhom2 during mammalian development is largely unclear. We have identified a spontaneous single gene deletion mutation of iRhom2 in Uncv mice. The iRhom2Uncv/Uncv mice exhibit hairless phenotype in a BALB/c genetic background...
2014: PloS One
https://www.readbyqxmd.com/read/25395669/genetic-interaction-implicates-irhom2-in-the-regulation-of-egf-receptor-signalling-in-mice
#20
Owen M Siggs, Adam Grieve, Hongmei Xu, Paul Bambrough, Yonka Christova, Matthew Freeman
iRhoms are closely related to rhomboid intramembrane proteases but lack catalytic activity. In mammals iRhoms are known to regulate the trafficking of TACE, the protease that cleaves the membrane bound inflammatory cytokine TNF. We have mapped a spontaneously occurring mouse mutation with a loss of hair phenotype, curly bare (cub), to the Rhbdf2 locus, which encodes the iRhom2 protein. The cub deletion removes the first 268 amino acids of the iRhom2 protein but is not a loss of function. We have also identified a previously reported suppressor of cub, called Mcub (modifier of curly bare), and find it to be a loss of function allele of the amphiregulin gene (Areg)...
November 13, 2014: Biology Open
keyword
keyword
96636
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"