Journal article
ADAM17 stabilizes its interacting partner inactive Rhomboid 2 (iRhom2) but not inactive Rhomboid 1 (iRhom1)
The Journal of biological chemistry, Vol.295(13), pp.4350-4358
03/27/2020
DOI: 10.1074/jbc.RA119.011136
PMID: 32060096
Abstract
The metalloprotease ADAM17 (a disintegrin and metalloprotease 17) is a key regulator of tumor necrosis factor α (TNFα), interleukin 6 receptor (IL-6R), and epidermal growth factor receptor (EGFR) signaling. ADAM17 maturation and function depend on the seven-membrane–spanning inactive rhomboid-like proteins 1 and 2 (iRhom1/2 or Rhbdf1/2). Most studies to date have focused on overexpressed iRhom1 and -2, so only little is known about the properties of the endogenous proteins. Here, we show that endogenous iRhom1 and -2 can be cell surface–biotinylated on mouse embryonic fibroblasts (mEFs), revealing that endogenous iRhom1 and -2 proteins are present on the cell surface and that iRhom2 also is present on the surface of lipopolysaccharide-stimulated primary bone marrow–derived macrophages. Interestingly, very little, if any, iRhom2 was detectable in mEFs or bone marrow–derived macrophages lacking ADAM17, suggesting that iRhom2 is stabilized by ADAM17. By contrast, the levels of iRhom1 were slightly increased in the absence of ADAM17 in mEFs, indicating that its stability does not depend on ADAM17. These findings support a model in which iRhom2 and ADAM17 are obligate binding partners and indicate that iRhom2 stability requires the presence of ADAM17, whereas iRhom1 is stable in the absence of ADAM17.
Details
- Title: Subtitle
- ADAM17 stabilizes its interacting partner inactive Rhomboid 2 (iRhom2) but not inactive Rhomboid 1 (iRhom1)
- Creators
- Gisela Weskamp - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York 10021Johanna Tüshaus - Institute for Advanced Study, Technical University Munich, 85748 Garching, GermanyDaniel Li - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York 10021Regina Feederle - German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, GermanyThorsten Maretzky - Inflammation Program and Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Steven Swendemann - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York 10021Erik Falck-Pedersen - Department of Biochemistry, Cellular and Molecular Biology, Weill Cornell Medicine, New York, New York 10021David R McIlwain - Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California 94305Tak W Mak - Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, CanadaJane E Salmon - Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, New York 10021Stefan F Lichtenthaler - Institute for Advanced Study, Technical University Munich, 85748 Garching, GermanyCarl P Blobel - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York 10021
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.295(13), pp.4350-4358
- DOI
- 10.1074/jbc.RA119.011136
- PMID
- 32060096
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000057, name: HHS | NIH | National Institute of General Medical Sciences, award: R01 GM64750, R35 GM134907; DOI: 10.13039/501100001659, name: Deutsche Forschungsgemeinschaft, award: FOR2290; name: Munich Cluster for Systems Neurology, award: EXC 2145 SyNergy
- Language
- English
- Date published
- 03/27/2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984066340602771
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