MARCH-IX mediates ubiquitination and downregulation of ICAM-1

  • FEBS Lett. 2007 Jan 9;581(1):45-51. doi: 10.1016/j.febslet.2006.11.075.
Simon Hoer  1 ,  Lorraine Smith ,  Paul J Lehner
Affiliations
  • 1. Department of Medicine, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
PMID: 17174307 DOI: 10.1016/j.febslet.2006.11.075
Abstract

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.