Overview
Dr. Griffin's research program is focused on understanding the functions of immunoproteasomes in cells of the immune system, particularly T cells. Immunoproteasomes are the dedicated proteasomes of the immune system and are responsible for most non-lysosomal intracellular protein degradation in these cells.
Immunoproteasomes play an important role in generating peptides for presentation by MHC class I molecules, but also appear to have other specific functions in T cells. We are using both transfected cells in culture and immunoproteasome subunit knockout mice as tools for elucidating these non-antigen processing functions. For example, T cells from mice deficient in two of the immunosubunits display hyper-proliferation in response to polyclonal stimuli. We are currently focused on elucidating the mechanism of this hyper-proliferation phenotype using such tools as nucleofection of primary T cells and gene expression analyses. We are also investigating the consequences of this phenotype on in vivo T cell responses, using stimulation with SEB super-antigen as a model, and on T cell-dependent autoimmune disease, using collagen-induced arthritis as a model.
Publications
Jayarapu, K, and TA Griffin. Protein-protein interactions among human 20S proteasome subunits and proteassemblin. Biochem. Biophys. Res. Comm. 314, 523-528 (2004).
De, M, Jayarapu, K, Elenich, L, Monaco, JJ, Colbert, RA, and TA Griffin. 2 propeptides influence cooperative proteasome assembly. J. Biol. Chem., 278, 6153-6159 (2003).
Prahalad, S, Kingsbury, DJ, Griffin, TA, Cooper, B-L, Glass, DN, Maksymowych, WP, and RA Colbert. Polymorphism in the MHC-encoded LMP7 gene: association with JRA without functional significance for immunoproteasome assembly. J. Rheum. 28, 2320-2325 (2001).
Griffin, TA, JP Slack, TS McCluskey, JJ Monaco, and RA Colbert. Identification of proteassemblin: a mammalian homologue of the yeast protein, Ump1p, that is required for normal proteasome assembly. Mol. Cell Biol. Res. Comm. 3, 212-217 (2000).
Kingsbury, DJ, TA Griffin, and RA Colbert. Novel propeptide function in proteasome assembly influences ß subunit composition. J. Biol. Chem. 275, 24156-24162 (2000).
