Differential regulation of G protein alpha subunit trafficking by mono- and polyubiquitination
Program in Systems Biology
GTP-Binding Protein alpha Subunits; Proteasome Endopeptidase Complex; Protein Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Ubiquitin
Previously we used mass spectrometry to show that the yeast G protein alpha subunit Gpa1 is ubiquitinated at Lys-165, located within a subdomain not present in other G alpha proteins (Marotti, L. A., Jr., Newitt, R., Wang, Y., Aebersold, R., and Dohlman, H. G. (2002) Biochemistry 41, 5067-5074). Here we describe the functional role of Gpa1 ubiquitination. We find that Gpa1 expression is elevated in mutants deficient in either proteasomal or vacuolar protease function. Vacuolar protease pep4 mutants accumulate monoubiquitinated Gpa1, and much of the protein is localized within the vacuolar compartment. In contrast, proteasome-defective rpt6/cim3 mutants accumulate polyubiquitinated Gpa1, and in this case the protein exhibits cytoplasmic localization. Cells that lack Ubp12 ubiquitin-processing protease activity accumulate both mono- and polyubiquitinated forms of Gpa1. In this case, Gpa1 accumulates in both the cytoplasm and vacuole. Finally, a Gpa1 mutant that lacks the ubiquitinated subdomain remains unmodified and is predominantly localized at the plasma membrane. These data reveal a strong relationship between the extent of ubiquitination and trafficking of the G protein alpha subunit to its site of degradation.
DOI of Published Version
Wang Y, Marotti LA Jr, Lee MJ, Dohlman HG. Differential regulation of G protein alpha subunit trafficking by mono- and polyubiquitination. J Biol Chem. 2005 Jan 7;280(1):284-91. doi 10.1074/jbc.M411624200. Link to article on publisher's site
The Journal of biological chemistry
Wang, Yuqi; Marotti, Louis A. Jr.; Lee, Michael J.; and Dohlman, Henrik G., "Differential regulation of G protein alpha subunit trafficking by mono- and polyubiquitination" (2005). Program in Systems Biology Publications and Presentations. 43.