A team of the Max-Planck Research Unit Enzymology of Protein Folding from Halle in cooperation with research teams of the Harvard University (Boston) and the University of Texas (Houston) shed light on the regulation of the cell cycle. Their findings appear in the Dec. 12. 1997 issue of Science and the results are expected to have considerable implications in the understanding of the mechanism of cell division.
The eukaryotic cell cycle is characterized by defined periods of preparation for chromosome replication (G1), DNA replication (S), preparation for mitosis (G2), and mitosis (M). Proper transition between these states require an evolutionarily highly conserved set of proline directed protein kinases. The overall principle underlying cell cycle regulation is the appropriately timed structural modification of proteins through kinase and phosphatase mediated phosphorylation/ dephosphorylation, and protein degradation.
The new results of the research teams suggest regulation
of mitotic progression via a novel mechanism involving
binding of a specialized protein (a so called peptidyl-prolyl
cis/trans isomerase) to phosphorylated mitotic proteins and
catalyzing a conformational change of these binding partners
thereby allowing the correct exit from mitosis. The authors
were able to show that this catalysis is extremely efficient
and that the recognition of the binding partners is sequence-
specific and extraordinary dependent on phosphorylation of
the target sequences. This consensus binding specificity has
been shown to correctly predict some novel isomerase targets.
Surprisingly, the target sequences are overlapping with
antigens recognized by a known mitosis-specific monoclonal
antibody. Moreover, the unique substrate specificity of the
essential mitotic isomerase has been rationalized based on
the crystal structure an
Contact: Mike Schutkowski