Research Awards
John Aletta, Ph.D.
University of Buffalo School of Medicine
"Post-Translational Modification of MeCP2 by Arginine Methylation"
2-Year Award: $95,120
Research Sponsor: Family and Friends of Jessie Lebson
Final Report (November 2004)
The function of the protein product of the MeCP2 gene is likely regulated by chemical modification in living cells. There is a distinct amino acid signature in the MeCP2 protein that is suggestive of modification by the addition of methyl groups to the amino acid arginine. The Aletta laboratory carried out experiments to determine if MeCP2 is indeed modified in intact cells by this means of chemical modification. The results demonstrate that three such methylation sites exist in MeCP2. The methylation occurs in living cells and can be increased by treatment with a class of neuronal growth factors known as neurotrophins. Whereas evidence from the Greenberg lab indicates that chemical modification by phosphorylation decreases MeCP2 binding to DNA, the effect of increased protein methylation of MeCP2 promotes DNA binding. Future experiments will be aimed at the examination of the complementary roles of protein methylation and phosphorylation in regulating the function of MeCP2 in neuronal gene expression.
John Aletta, Ph.D.University of Buffalo School of Medicine
"Post-Translational Modification of MeCP2 by Arginine Methylation"
2-Year Award: $95,120
Research Sponsor: Family and Friends of Jessie Lebson
Final Report (November 2004)
The function of the protein product of the MeCP2 gene is likely regulated by chemical modification in living cells. There is a distinct amino acid signature in the MeCP2 protein that is suggestive of modification by the addition of methyl groups to the amino acid arginine. The Aletta laboratory carried out experiments to determine if MeCP2 is indeed modified in intact cells by this means of chemical modification. The results demonstrate that three such methylation sites exist in MeCP2. The methylation occurs in living cells and can be increased by treatment with a class of neuronal growth factors known as neurotrophins. Whereas evidence from the Greenberg lab indicates that chemical modification by phosphorylation decreases MeCP2 binding to DNA, the effect of increased protein methylation of MeCP2 promotes DNA binding. Future experiments will be aimed at the examination of the complementary roles of protein methylation and phosphorylation in regulating the function of MeCP2 in neuronal gene expression.