Dieter H. Wolf

Prof. Dr. Dieter H. Wolf

(Director of the Institute)

Pfaffenwaldring 55
D-70569 Stuttgart
Germany
Tel.:+49-(711)-685-64390; Fax: -64392
e-mail: dieter.wolf[at]ibc.uni-stuttgart.de
PublicationsDeputy-Coordidator of the EC Network of Excellence RUBICON: "Role of Ubiquitin and Ubiquitin-like Modifiers in Cellular Regulation"

Research of the Institute of Biochemistry focusses on the important questions concerning cellular regulation. Protein transport, protein folding and protein stability play a central role. The protein degrading systems of the eukoryotic cell, the proteasome and the lysosome, are under intensive investigation. Research includes also the processes of protein flow to these degradation systems, such as endocytosis leading to the lysosome, and retrograde protein transport from the endoplasmic reticulum, which ends in the cytoplasmic proteasome. Ions, like Mn2+ and Ca2+ as well as their transporters play an important role in the control of these and many other cellular processes. This makes them also a research target.

HISTORICAL ASPECTS

The Wolf group has a long-standing interest in the physiological function of intracellular proteolysis in eukaryotes. As research organism the yeast Saccharomyces cerevisiae is used which constitutes a paradigm and genetic model organism for eukaryotic cells and is therefore an ideal system to unravel the network of life.

 First research was directed towards lysosomal (yeast: vacuole) proteolysis. In 1975 (J. Bacteriol. 123, 1150-1156), the first proteinase-defective mutant of yeast was isolated and characterized. In 1989 (J. Biol. Chem. 264, 16037-16045 ), the major function of vacuolar proteolysis in cell differentiation and cell survival under starvation conditions was solved.

Genetically engineered vacuolar proteinase mutants led to the discovery of autophagocytosis in yeast and allowed the Wolf group the identification of new, specific proteinases (J. Biol. Chem. 259, 13334-13343 [1984]), among them the first specific hormone processing enzymes (EMBO J. 4, 173-177 [1985]). Furthermore, the yeast proteasome was discovered (J. Biol. Chem. 259, 13344-13348 [1984]).

The discovery of the involvement of the proteasome in the degradation of ubiquitinated proteins in vivo by the Wolf group in 1991 (EMBO J. 10, 555-562) marked a seminal progress in the understanding of the,- since then termed -,   ubiquitin-proteasome system  UPS) in regulated cellular proteolysis. The composition of the eukaryotic 20S core of the proteasome consisting of 14 subunits was unraveled (Biochemistry 33, 12229-12237 [1994]) and its three different active site subunits were genetically dissected (J. Biol. Chem. 272, 25200-25209 [1997]).

As one of the first UPS regulated metabolic processes, glucose triggered catabolite degradation of the gluconeogenetic enzyme fructose-1,6-bisphosphatase (FBPase) was uncovered (Nature 369, 283-284 [1994]; J. Biol. Chem. 270, 26446-26450 [1995]).

In 1996 (Science 273, 1725-1728), the Wolf group discovered the retrotranslocation of a misfolded, fully glycosylated lumenal protein ( CPY* ) of the endoplasmic reticulum (ER) back into the cytoplasm and its degradation via the ubiquitin-proteasome system (ERAD). CPY* as a model substrate of ER protein quality control and degradation (ERQD) was established. The 1996 Science publication, which made a dogma fall and opened a new field of research, was considered a landmark paper of cell biology (Landmark Papers in Yeast Cell Biology, P. Linder, D. Shore and M. N. Hall, eds., pp. 273-274, Cold Spring Harbor Laboratory Press [2006]).