TY - JOUR
T1 - Novel functions of inactive rhomboid proteins in immunity and disease
AU - Geesala, Ramasatyaveni
AU - Issuree, Priya D.
AU - Maretzky, Thorsten
N1 - Funding Information:
Support was provided in part by the American Cancer Society (Award Number ACS-IRG-15-176-41) and by the Carver College of Medicine, University of Iowa Research Start-Up Funds to T.M.
Publisher Copyright:
©2019 Society for Leukocyte Biology
PY - 2019/10/1
Y1 - 2019/10/1
N2 - iRhoms are related to a family of intramembrane serine proteinases called rhomboids but lack proteolytic activity. In mammals, there are two iRhoms, iRhom1 and iRhom2, which have similar domain structures and overlapping specificities as well as distinctive functions. These catalytically inactive rhomboids are essential regulators for the maturation and trafficking of the disintegrin metalloprotease ADAM17 from the endoplasmic reticulum to the cell surface, and are required for the cleavage and release of a variety of membrane-associated proteins, including the IL-6 receptor, l-selectin, TNF, and EGFR ligands. iRhom2-dependent regulation of ADAM17 function has been recently implicated in the development and progression of several autoimmune diseases including rheumatoid arthritis, lupus nephritis, as well as hemophilic arthropathy. In this review, we discuss our current understanding of iRhom biology, their implications in autoimmune pathologies, and their potential as therapeutic targets.
AB - iRhoms are related to a family of intramembrane serine proteinases called rhomboids but lack proteolytic activity. In mammals, there are two iRhoms, iRhom1 and iRhom2, which have similar domain structures and overlapping specificities as well as distinctive functions. These catalytically inactive rhomboids are essential regulators for the maturation and trafficking of the disintegrin metalloprotease ADAM17 from the endoplasmic reticulum to the cell surface, and are required for the cleavage and release of a variety of membrane-associated proteins, including the IL-6 receptor, l-selectin, TNF, and EGFR ligands. iRhom2-dependent regulation of ADAM17 function has been recently implicated in the development and progression of several autoimmune diseases including rheumatoid arthritis, lupus nephritis, as well as hemophilic arthropathy. In this review, we discuss our current understanding of iRhom biology, their implications in autoimmune pathologies, and their potential as therapeutic targets.
KW - a disintegrin and metalloprotease 17 (ADAM17)
KW - epidermal growth factor receptor (EGFR)
KW - inactive rhomboid 1 (iRHOM1)
KW - inactive rhomboid 2 (iRHOM2)
KW - rhomboid 5 homolog 1 (RHBDF1)
KW - rhomboid 5 homolog 2 (RHBDF2)
KW - tumor necrosis factor (TNF)
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U2 - 10.1002/JLB.3VMR0219-069R
DO - 10.1002/JLB.3VMR0219-069R
M3 - Review article
C2 - 31369701
AN - SCOPUS:85070090413
SN - 0741-5400
VL - 106
SP - 823
EP - 835
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 4
ER -