MARCH-IX mediates ubiquitination and downregulation of ICAM-1.
The membrane associated RING-CH (MARCH) family of genes encode a novel group of RING-type ubiquitin E3 ligases. Overexpression of one of these family members, MARCH-IX, leads to a downregulation of cell surface major histocompatibility complex (MHC) class I and CD4. Here, we identify MARCH-IX as the first ubiquitin E3 ligase to control expression of the critical cell adhesion molecule ICAM-1. MARCH-IX expression causes ubiquitination and downregulation of ICAM-1 and a short alternative transcript of MARCH-IX lacking the RING-CH domain, termed MARCH-IX RINGless, is shown to act as a positive regulator of MARCH-IX activity.
Hoer
Simon
S
Department of Medicine, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
Smith
Lorraine
L
Lehner
Paul J
PJ
D017398:Alternative Splicing / Q000502:physiology; D015704:CD4 Antigens / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D015704:CD4 Antigens; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012333:RNA, Messenger; D025801:Ubiquitin; D018799:Intercellular Adhesion Molecule-1; C517365:MARCHF9 protein, human; D044767:Ubiquitin-Protein Ligases