This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The major goal of this application is to study the function of a novel family of membrane-associated RING-CH (MARCH) proteins in receptor downregulation, particularly with respect to the ubiquitin-mediated lysosomal targeting of endocytosed major histocompatibility complex (MHC) class I and CD4 molecules. MARCH proteins are cellular homologues of the viral K3-family of immune evasion proteins found in poxviruses and gamma-2 herpesviruses.
Specific Aim 1 : The role of ubiquitination and MARCH proteins for MHC I and CD4 degradation. We proposed to study ubiquitin-mediated internalization and degradation of MHC I molecules in the highly endocytic cell line KG-1 and internalization of CD4 in the T cell line CEM.
Specific Aim 2 : To identify other transmembrane proteins regulated by MARCH proteins. To identify additional transmembrane proteins that are downregulated upon overexpression or stabilized in the absence of MARCH proteins, we proposed to use proteomic approaches.
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