Palmitoylation is one of several different lipid modifications that serve to target and anchor proteins to membranes in eukaryotic cells. Palmitoylation has been long-recognized for its role in directing the localization of a variety of signaling proteins, including key players in cancer like H- and K-Ras, Src, Lck, and Rho, to plasma membrane sites of action. Despite the long history, little has been learned regarding the enzymology of this modification - the responsible enzymatic activities have not been identified. Our recent work in the yeast Saccharornyces cerevisiae, indicates that the ankyrin-repeat protein Akr1p is required for palmitoylation and consequent membrane localization of the type I casein kinase, Yck2p; in akr1delta cells, Yck2p is not palmitoylated and as a consequence is mislocalized diffusely throughout the cytoplasm, rather than to the plasma membrane. The major goal of this proposal is to characterize the role of Akr1p in the palmitoylation process. Preliminary work indicates that Akr1p is a strong candidate to be an enzymatic component of the palmitoyl transferase. This will be tested. In addition, Akr1p-containing complexes will be purified from yeast to identify the proteins that collaborate with Akr1p for palmitoylation. Another significant fact regarding Akr1p is that is its closest human homolog is a protein identified for its possible role in Huntington's disease. Thus, these fundamental studies on the function of Akr1p in yeast may well impact our understanding of the disease processes in both cancer and in Huntington's disease.
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| Roth, Amy F; Papanayotou, Irene; Davis, Nicholas G (2011) The yeast kinase Yck2 has a tripartite palmitoylation signal. Mol Biol Cell 22:2702-15 |
| Huang, Kun; Sanders, Shaun S; Kang, Rujun et al. (2011) Wild-type HTT modulates the enzymatic activity of the neuronal palmitoyl transferase HIP14. Hum Mol Genet 20:3356-65 |
| Papanayotou, Irene; Sun, Beimeng; Roth, Amy F et al. (2010) Protein aggregation induced during glass bead lysis of yeast. Yeast 27:801-16 |
| Conibear, Elizabeth; Davis, Nicholas G (2010) Palmitoylation and depalmitoylation dynamics at a glance. J Cell Sci 123:4007-10 |
| Huang, Kun; Kang, Martin H; Askew, Caitlin et al. (2010) Palmitoylation and function of glial glutamate transporter-1 is reduced in the YAC128 mouse model of Huntington disease. Neurobiol Dis 40:207-15 |
| Kang, Rujun; Wan, Junmei; Arstikaitis, Pamela et al. (2008) Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation. Nature 456:904-9 |
| Wan, Junmei; Roth, Amy F; Bailey, Aaron O et al. (2007) Palmitoylated proteins: purification and identification. Nat Protoc 2:1573-84 |
| Roth, Amy F; Wan, Junmei; Bailey, Aaron O et al. (2006) Global analysis of protein palmitoylation in yeast. Cell 125:1003-13 |
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