Jump to ContentJump to Main Navigation

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

12 Issues per year

VolumeIssuePage

Issues

An essential role for Pin1 in Xenopus laevis embryonic development revealed by specific inhibitors

Dirk Wildemann1 / Birte Hernandez Alvarez2 / Gerlind Stoller3 / Xiao Zhen Zhou4 / Kun Ping Lu5 / Frank Erdmann6 / David Ferrari7 / Gunter Fischer8

1Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120 Halle/Saale, Germany
Authors 1 and 2 contributed equally to this work.

2Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120 Halle/Saale, Germany and present address: Max Planck Institute for Developmental Biology, Department Protein Evolution, Spemannstrasse 35, D-72076 Tübingen, Germany.

3Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120 Halle/Saale, Germany

4Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA

5Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA

6Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120 Halle/Saale, Germany

7Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120 Halle/Saale, Germany

8Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120 Halle/Saale, Germany

Corresponding author

Citation Information: Biological Chemistry. Volume 388, Issue 10, Pages 1103–1111, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: 10.1515/BC.2007.127, October 2007

Publication History

Received:
2007-03-14
Accepted:
2007-06-25
Published Online:
2007-10-16

Abstract

The peptidyl prolyl cis/trans isomerase (PPIase) Pin1 plays an important role in phosphorylation-dependent events of the cell cycle. This function is linked to its display of two phosphothreonine/phosphoserine-proline binding motifs, one within the type IV WW domain and a second within the parvulin-like catalytic domain. By microinjection of the compound Ac-Phe-D-Thr(PO3H2)-Pip-Nal-Gln-NH2, which inhibits Xenopus laevis Pin1 with a K i value of 19.4±1.5 nM, into the animal pole of X. laevis embryos at the two-cell stage, the impact of Pin1 PPIase activity on cell cycle progression and embryonic development could be analysed, independent of WW domain-mediated phosphoprotein binding. Injected embryos showed a dramatically decreased survival rate at late stages of development that could only be partially compensated by co-injection with mRNAs of enzymatically active Pin1 variants, demonstrating that the phosphorylation-specific PPIase activity of Pin1 is essential for cell division and development in X. laevis.

Keywords: embryonic development; inhibition; microinjection; peptidyl prolyl cis/trans isomerase (PPIase); phosphopeptide

Comments (0)

Please log in or register to comment.