An essential role for Pin1 in Xenopus laevis embryonic development revealed by specific inhibitors.
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 Ki 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.
Wildemann
Dirk
D
Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120 Halle/Saale, Germany.
Hernandez Alvarez
Birte
B
Stoller
Gerlind
G
Zhou
Xiao Zhen
XZ
Lu
Kun Ping
KP
Erdmann
Frank
F
Ferrari
David
D
Fischer
Gunter
G
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
D004791:Enzyme Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009842:Oligopeptides; D029867:Xenopus Proteins; C525405:acetyl-phenylalanyl-phosphothreonyl-piperidine-2-carboxylic acid-2-naphthylalanyl-glutaminamide; D019696:Peptidylprolyl Isomerase; C525404:Pin1 protein, Xenopus