An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release.
The type I, 55-kDa tumor necrosis factor receptor (TNFR1) is released to the extracellular space by two mechanisms, the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains. Both pathways appear to be regulated by an interaction between TNFR1 and ARTS-1 (aminopeptidase regulator of TNFR1 shedding). Here, we sought to identify ARTS-1-interacting proteins that modulate TNFR1 release. Co-immunoprecipitation identified an association between ARTS-1 and RBMX (RNA-binding motif gene, X chromosome), a 43-kDa heterogeneous nuclear ribonucleoprotein. RNA interference attenuated RBMX expression, which reduced both the constitutive release of TNFR1 exosome-like vesicles and the IL-1beta-mediated inducible proteolytic cleavage of soluble TNFR1 ectodomains. Reciprocally, over-expression of RBMX increased TNFR1 exosome-like vesicle release and the IL-1beta-mediated inducible shedding of TNFR1 ectodomains. This identifies RBMX as an ARTS-1-associated protein that regulates both the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains.
Adamik
Barbara
B
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 6D03, MSC 1590, Bethesda, MD 20892-1590, USA.
Islam
Aminul
A
Rouhani
Farshid N
FN
Hawari
Feras I
FI
Zhang
Jing
J
Levine
Stewart J
SJ
D000626:Aminopeptidases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D053583:Interleukin-1beta / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D034622:RNA Interference; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D053583:Interleukin-1beta; D015778:Minor Histocompatibility Antigens; C510272:RBMX protein, human; D047888:Receptors, Tumor Necrosis Factor, Type I; D000626:Aminopeptidases; C464841:ERAP1 protein, human