Posttranscriptional Control of Expression Localization, Functional ...

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The Journal of Immunology

Discrete Domains of MARCH1 Mediate Its Localization, Functional Interactions, and Posttranscriptional Control of Expression1 Maurice Jabbour,* Erin M.Campbell,† Hanna Fares,† and Lonnie Lybarger2*‡ Within APCs, ubiquitination regulates the trafficking of immune modulators such as MHC class II and CD86 (B7.2) molecules. MARCH1 (membrane-associated RING-CH), a newly identified ubiquitin E3 ligase expressed in APCs, ubiquitinates MHC class II, thereby reducing its surface expression. Following LPS-induced maturation of dendritic cells, MARCH1 mRNA is down-regulated and MHC class II is redistributed to the cell surface from endosomal compartments. Here, we show that MARCH1 expression is also regulated at the posttranscriptional level. In primary dendritic cell and APC cell lines of murine origin, MARCH1 had a half-life of