Major Achievements of the Wolf Laboratory in the Past (175 Publications)
Isolation of the first proteinase mutant of yeast for starting a study on the
function of intracellular proteolysis, an at the time neglected field of research (J. Bacteriol.
(1975) 123, 1150-1156).
1977 - 1988
Discovery of many novel proteinases of yeast, among those hormone (pheromone)
processing enzymes (EMBO J. (1985) 4, 173-177) and proteinase yscE, the yeast proteasome (J. Biol.
Chem. (1984) 259, 13344-13348).
Discovery of the vacuolar (lysosomal) proteinases of yeast as essential
catalysts for massive protein degradation under starvation as well as for cell differentiation
(sporulation) and cell survival (J. Biol. Chem. (1989) 264, 16037-16045).
Discovery of the proteasome as the essential proteinase of the
ubiquitin-triggered degradation pathway of proteins in the cell (
in vivo) (EMBO J. (1991) 10, 555-562). Since then the term „ubiquitin-proteasome pathway“
(UPS) is used.
Degradation of proteins in denatured state in the inner cavity of the
cylinder of the proteasome (instead of on the outer surface, as proposed) is predicted (Mol.
Microbiol. (1992) 6, 2437-2442).
1991 – 1994
The genes of most 20S core subunits of the proteasome are identified and
analyzed (Biochemistry (1994) 33, 12229-12237).
A first indication that the proteasome might be invoved in cell cycle
regulation is provided (FEBS Lett. (1993) 336, 34-36).
Autophagcytosis mutants of yeast are isolated (FEBS Lett. (1994) 349,
Degradation of the first regulatory enzyme (fructose-1,6-bisphosphatase) by
the proteasome in the cell is discovered (Nature (1994) 369, 283-284).
Retrograde transport of a fully glycosylated misfolded protein across the
membrane of the endoplasmic reticulum into the cytoplasm and its ubiquitination and degradation by
the proteasome is discovered. This finding makes the dogma fall that proteins, once imported into
the ER will never return back into the cytosol. The finding discloses the basic mechanism of
ER-associated protein degradation (Science (1996) 273, 1725-1728; Highlighted in: „Landmark Papers
in Yeast Biology“ (P. Lindner, D. Shore, M. N. Hall, eds.) Cold Spring Harbor Laboratory Press
2006). With Der1 the first specific component of the ER-associated protein degradation pathway is
discovered (EMBO J. (1996) 15, 753-763). Furthermore, N-glycosylation as a crucial determinant for
ER-associated protein degradation is disclosed (Yeast (1996) 12, 1229-1238).
The active sites and their autocatalytic activation in the proteasome is
uncovered (J. Biol. Chem. (1997) 272, 25200-25209).
Membrane topology and function as a ubiquitin ligase of ER-localized
Der3/Hrd1 is uncovered (J. Biol. Chem. (2001) 276, 10663-10669).
Discovery of the Gid complex as a novel RING ubiquitin ligase involved in
regulation of carbohydrate metabolism. The orthologous Muskelin/CTLH complex is proposed to be the
mammalian counterpart (Mol. Biol. Cell (2008) 19, 3323-3333).
Discovery of the N-end rule ubiquitin ligase Ubr1 as the E3 directing
misfolded proteins of the cytoplasm to polyubiquitination and proteasomal degradation (FEBS Lett.
(2008) 582, 4143-4146).
The topology of the seven-membered Gid ubiquitin ligase complex is unraveled
(J. Biol. Chem. (2012) 287, 25602-25614).
The cytoplasmic ubiquitin ligase Ubr1 is discovered as an additional ligase
ubiquitinating misfolded membrane proteins of the endoplasmic reticulum under stress and in the
absence of the canonical ER ligases. The finding links ER-associated protein degradation with
cytoplasmic protein quality control. (Proc. Natl. Acad. Sci. USA (2013) 110, 15271-15276).