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.
MeSH terms
-
Alternative Splicing / physiology
-
CD4 Antigens / metabolism
-
Down-Regulation / physiology
-
Enzyme Activation / physiology
-
HeLa Cells
-
Histocompatibility Antigens Class I / metabolism
-
Humans
-
Intercellular Adhesion Molecule-1 / genetics
-
Intercellular Adhesion Molecule-1 / metabolism*
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Protein Structure, Tertiary / physiology
-
RNA, Messenger / biosynthesis
-
RNA, Messenger / genetics
-
Ubiquitin / metabolism*
-
Ubiquitin-Protein Ligases / biosynthesis*
-
Ubiquitin-Protein Ligases / genetics
-
Ubiquitin-Protein Ligases / metabolism
Substances
-
CD4 Antigens
-
Histocompatibility Antigens Class I
-
Membrane Proteins
-
RNA, Messenger
-
Ubiquitin
-
Intercellular Adhesion Molecule-1
-
MARCHF9 protein, human
-
Ubiquitin-Protein Ligases