posted on 2012-11-06, 00:00authored byAyuko Kimura, Yu Kato, Hisashi Hirano
The 26S proteasome is a large, complex multisubunit protease
involved
in protein quality control and other critical processes in eukaryotes.
More than 110 post-translational modification (PTM) sites have been
identified by a mass spectrometry of the 26S proteasome of Saccharomyces cerevisiae and are predicted to be implicated
in the dynamic regulation of proteasomal functions. Here, we report
that the N-myristoylation of the Rpt2 subunit controls the intracellular
localization of the 26S proteasome. While proteasomes were mainly
localized in the nucleus in normal cells, mutation of the N-myristoylation
site of Rpt2 caused diffusion of the nuclear proteasome into the cytoplasm,
where it formed aggregates. In mutant cells, the level of accumulation
of cytoplasmic proteasomes was significantly increased in the nonproliferating
state. Although the molecular assembly and peptidase activity of the
26S proteasome were totally unchanged in the nonmyristoylated mutants
of Rpt2, an increased level of accumulation of polyubiquitinated proteins
and a severe growth defect were observed in mutant cells induced for
protein misfolding. In addition, polyubiquitinated protein and the
nuclear protein Gcn4 tended not to colocalize with the proteasome
in normal and mutant cells. Our results suggest that N-myristoylation
is involved in regulating the proper intracellular distribution of
proteasome activity by controlling the nuclear localization of the
26S proteasome.