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Alexander Amerik, Ph.D.

Amerik Lab
PUBLICATIONS

1. Amerik A.Yu., Sindhi N., Hochstrasser M. (2006). A conserved late endosome-targeting signal required for Doa4 deubiquitinating enzyme function. J. Cell Biol. 175: 825-835.

2. Amerik A. Yu. and Hochstrasser M. (2004). Mechanism and function of deubiquitinating enzymes. Biochim. Biophys. Acta. 1695 (1-3): 189-207.

3. Amerik A.Yu., Novak J., Swaminathan S., Hochstrasser M. (2000). The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol. Biol. Cell 11: 3365-3380.

4. Amerik A.Yu.,  Li S.-J., Hochstrasser M. (2000). Analysis of the deubiquitinating enzymes of the yeast Saccharomyces cerevisiae. Biol. Chem. 381: 981-992.

5. Hochstrasser M., Jonson P.R., Arendt C.S., Amerik A. Yu,  Swaminathan S., Swanson R., Li  S. J., Laney J., Pals-Rylaarsdam R., Nowak J., Connery P. (1999).  The Saccharamyces cerevisiae ubiquitin-proteasome system.  Philos. Trans. R. Lond. B. Biol. Sci. 354: 1513-1522.

6. Swaminathan S., Amerik A.Yu., Hochstrasser M. (1999).  The Doa4 deubiquitinating enzyme is required for ubiquitin homeostasis in yeast. Mol. Biol. Cell 10: 2583-2594.

7. Papa F.R., Amerik A.Yu., Hochstrasser M.  (1999). Interaction of Doa4 deubiquitinating enzyme with the yeast 26S proteasome. Mol. Biol. Cell 10: 741-756.

8. Lindsey D.F., Amerik A.Yu., Deery W.J., Bishop J.D., Hochstrasser M., Gomer R.H.  (1998). A deubiquitinating enzyme that disassembles free polyubiquitin chains is required for development but not growth of Dictyostelium. J. Biol. Chem. 273:  29178-29187.

9. Amerik A.Yu.,  Swaminathan S., Krantz B., Wilkinson K., Hochstrasser M.  (1997).  In vivo disassembly of free polyubiquitin chains by yeast Ubp14 modulates rates of protein degradation by the proteasome. EMBO Journal 16: 4826-4838

10. Dergousova N.I., Amerik A.Yu., Volynskaya A.M., Rumsh L.D. (1996).  HIV-1 protease. Cloning, expression and purification. Appl. Biochem. and Biotechn. 61: 97-107.

11. Hochstrasser M., Papa F., Chen P., Swaminathan S., Johnson P., Amerik A., Li S.-J. (1995).  The DOA pathway: Studies on the functions and mechanisms of ubiquitin-dependent protein degradation in yeast Saccharomyces cerevisiae. Cold Spring Harbor Symp. Quant. Biol. 60: 503-513.

12. Amerik A.Yu., Antonov V.K., Gorbalenya A.E., Kotova S.A., Rotanova T.V., Simbarevich E.V.  (1991). Site-directed mutagenesis of La protease. Catalytically active serine residue. FEBS Letters  287:  211-214.

 
 
LAB MEMBERS

Alexander Amerik , Principal Investigator

 
ROTATION PROJECTS

Analysis of the yeast deubiquitinating enzymes*

#1 - Affinity purification of the yeast protein complexes containing deubiquitinating enzyme Doa4.

Doa4 is a critical player in ubiquitin homeostasis in the yeast Saccharomyces cerevisiae. We have found that Doa4 is involved in ubiquitin recycling at the 26S proteasome and at the cytoplasmic face of the late endosome. We believe that the enzymatic activity of Doa4 must be thoroughly regulated. Otherwise, uncontrolled deubiquitination may have critical consequences for eukaryotic cell. Conceivably, regulation of Doa4 occurs at the levels of interaction with protein cofactors. The major goal of this project is to identify Doa4 partners in yeast. The results will be important for understanding the mechanistic details of how Doa4 functions in vivo.

#2 – Analysis of the molecular basis for genetic interaction between mutations in deubiquitinating enzyme Doa4 and class E vacuolar protein sorting factors.

Inactivation of the class E vacuolar protein factors leads to efficient suppression of the doa4 mutant phenotypes. To determine the mechanisms of this suppression, we plan to conduct a mutant screen based on the mini-Tn3 transposon-mutagenized library. We expect that this approach will identify deubiquitinating enzymes that are involved, along with Doa4, in membrane protein trafficking in yeast.

*Deubiquitinating enzymes are highly specific proteases that remove ubiquitin (a small protein that modifies substrate proteins) from ubiquitin-protein conjugates and are responsible for processing of ubiquitin precursors.