Dana W. AswadProfessor, Molecular Biology and Biochemistry |
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Research Interests |
Regulation of protein function and gene expresssion by post-translational modification. Biochemistry of protein damage, aging, and repair. Biochemical characterization of protein pharmaceuticals. | |
| URL | www.faculty.uci.edu/scripts/UCIFacultyProfiles/detailMBB.cfm?ID=2135 | |
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Academic Distinctions |
NIH Research Career Development Award. Editorial Board, The Journal of Biological Chemistry |
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Research Abstract |
Post-translational modification serves as an important mechanism for modulating the structure, activity and lifetime of many proteins. My laboratory is exploring two distinct areas related to post-translational modification. One line of research concerns the cellular function of protein L-isoaspartyl methyltransferase (PIMT), an enzyme that methylates damaged proteins that contain atypical isoaspartyl residues. Substantial evidence indicates that this enzyme serves to repair these atypical residues by converting the isopeptide bond to a normal peptide bond. Current research is focused on testing the repair hypothesis in cell culture systems and PIMT-knockout mice, determining the medical consequences of PIMT deficiency in humans, and exploring the possibility that isoaspartyl sites in certain extracellular matrix proteins of the brain may play a role in development. A second line of research concerns the function and substrate specificity of protein methyltransferases that modify arginine in proteins. Arginine methylation appears to play an important role in modulating the interactions of proteins with nucleic acids. We are currently investigating the role of protein-arginine methylation in the regulation of gene expression, with an emphasis on the identification and characterization of endogenous substrates for PRMT4 (protein arginine methyltransferase 4; also known as CARM1 (coactivator-associated arginine methyltransferase 1)). Patents: "Determination of Isoaspartate in Proteins" United States Patent No. 5,273,886; issued Dec. 28, 1993. |
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| Publications | Khoury MK, Parker I and Aswad DW (2009) Aquisition of chemiluminescent signals from immunoblots with a digital SLR camera. Analyt. Biochem., in press. | |
| Carter WG and Aswad DW (2008) Formation, localization, and repair of L-isoaspartyl sites in histones H2A and H2B in nucleosomes from rat liver and chicken erythrocytes. Biochemistry 47, 10757-64. | ||
| Zhu, JX and Aswad, DW (2007) Selective cleavage of isoaspartyl peptide bonds by hydroxylamine after methyltransferase priming. Analyt. Biochem. 364, 1-7. | ||
| Zhu JX, Doyle HA, Mamula MJ, Aswad DW. (2006) Protein repair in the brain: proteomic analysis of endogenous substrates for protein L-isoaspartyl methyltransferase in mouse brain. J Biol Chem. 281,33802-13. | ||
| Reissner KJ, Paranandi MV, Luc TM, Doyle HA, Mamula MJ, Lowenson JD, and Aswad DW (2006) Synapsin I is a major endogenous substrate for protein L-isoaspartyl methyltransferase in mammalian brain. J. Biol. Chem. 281, 8389-98. | ||
| Yang ML, Doyle HA, Gee RJ, Lowenson JD, Clarke S, Lawson BR, Aswad DW, Mamula MJ. (2006) Intracellular protein modification associated with altered T cell functions in autoimmunity. J Immunol. 177, 4541-9. | ||
| Young, G.W, Hoofring, S.A., Mamula, M.J., Doyle, H.A., Bunick, G.J., Hu, Y. and Aswad, D.W (2005) Protein L-isoaspartyl methyltransferase catalyzes in vivo racemization of aspartate-25 in mammalian histone H2B. J. Biol. Chem. 280, 26094-98. | ||
| Reissner, K. J. and Aswad, D.W. (2003) Deamidation and isoaspartate formation in proteins: unwanted alterations or surreptitious signals? Cell. Molec. Life Sci. 60, 1281-95. | ||
| Li, H., Park, S., Kilburn, B., Jelinek, M. A., Henschen-Edman, A., Aswad, D. W., Stallcup, M. R. and Laird-Offringa, I. A. (2002) Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. J. Biol. Chem. 277, 44623-30. | ||
| Young, A.L., Carter, W.G., Doyle, H.A., Mamula, M.J. and Aswad, D.W. (2001) Structural integrity of histone H2B in vivo requires the activity of protein L-isoaspartyl methyltransferase, a putative protein repair enzyme. J. Biol. Chem. 276, 37161-37165. | ||
| Schurter, B.T., Koh, S.S., Chen, D., Bunick, G.J., Harp, J.M., Hanson, B.L., Henschen-Edman, A., Mackay, D. R., Stallcup, M. R., and Aswad, D.W. (2001) Methylation of histone H3 by coactivator-associated arginine methyltransferase 1. Biochemistry 40, 5747-5756. | ||
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Professional Society |
American Society for Biochemistry and Molecular
Biology
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| Graduate Programs |
Cell Biology Neurobiology Structural Biology and Molecular Biophysics Biotechnology |
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| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=2135 | |
| Last updated | 09/28/2009 | |