Abstracts
Résumé
Pin1 est une peptidyl-prolyl isomérase (PPIase) catalysant l’isomérisation cis/trans de certains liens peptidiques précédant une proline. L’impact d’une telle modification peut représenter un changement structural important et impliquer une modulation des propriétés d’une protéine. Pin1 est impliquée à différents stades du cycle cellulaire et est nécessaire à l’entrée en mitose. Parmi les cibles de Pin1, plusieurs protéines comme p53, Cdc25C, Myt1 et Wee1 sont associées au cycle cellulaire, d’autres comme Rpb1 et Spt5 sont impliquées dans la transcription. Une autre cible de Pin1, la protéine tau, joue un rôle déterminant dans la pathogénie de la maladie d’Alzheimer. Le rôle précis de l’interaction de Pin1 avec ses cibles reste encore méconnu. Cependant, un nouveau mécanisme semble émerger, dans lequel Pin1 jouerait un rôle de modulateur de la déphosphorylation de certaines protéines par des phosphatases trans-spécifiques
Abstract
Peptidyl-prolyl isomerases (PPIases) are chaperone enzymes which alter the peptide bond between a given amino acid and a proline, changing it from the cis to the trans conformation and vice versa. This modification can cause dramatic structural modifications which can affect the properties of targeted proteins. The ubiquitous PPIase Pin1, conserved from yeast to human, has been shown to be necessary for entry into mitosis. The yeast homologue, Ess1, is essential for cell survival. Pin1 possesses a WW domain which specificaly recognizes pSer-Pro and pThr-Pro motifs in which the first amino acid is phosphorylated. Pin1 binds to many proteins implicated in cell cycle regulation (e.g. p53, Myt1, Wee1, and Cdc25C). Pin1 also targets tau, a protein forming part of the neuronal cytoskeleton which is hyperphosphorylated in patients suffering from Alzheimer’s disease (AD). Pin1 could, therefore, be involved in the pathogenesis of AD. Furthermore, Pin1 also binds two proteins involved in transcription: Rpb1, the largest subunit of RNA polymerase II and Spt5, a regulator of the elongation of transcription. Both these proteins possess domains rich in S/T-P motifs which can be targeted by Pin1 when phosphorylated. Recent studies show that Pin1 modulates the dephosphorylation of some proteins by allowing trans-specific phosphatases to recognize their target after isomerization. This unexpected role might allow protein regulation via peptidyl-prolyl isomerase activity.
Appendices
Références
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