Journal of Cell Science 116, e502-e502 (2003)
Copyright © 2003 The Company of Biologists Limited
The Pin1 cancer catalyst
Phosphorylation of S/T-P motifs in proteins by proline-directed kinases
(e.g. MAP kinases) is a major signalling mechanism. Some of the resulting
phosphoproteins become substrates for the peptidyl-prolyl cis/trans isomerase
Pin1; this provides a further level of regulation by inducing conformational
changes that can have a profound effect on the activity, localization,
phosphorylation status and stability of the protein. In a Commentary on
p. 773, Kun Ping Lu and
co-workers review work that indicates that Pin1 is a key regulator of cell
proliferation. Depletion of Pin1 can cause mitotic arrest and apoptosis, and
the enzyme has been shown to regulate synthesis of cyclin D1. Pin1 appears to
target the transcription factor JUN and ß-catenin, both of which activate
the cyclin D1 promoter, and studies of Pin1-null mice have
revealed that Pin1 directly stabilizes cyclin D protein. Furthermore, recent
work shows that Pin1 also regulates the tumour suppressor p53 as part of the
DNA damage response. Since Pin1 is expressed in several cancers, Lu and
co-workers go on to discuss its potential as a target for anti-cancer therapy,
suggesting that its high specificity makes it an attractive option.
Related articles in JCS:
- Prolyl isomerase Pin1: a catalyst for oncogenesis and a potential therapeutic target in cancer
- Akihide Ryo, Yih-Cherng Liou, Kun Ping Lu, and Gerburg Wulf
JCS 2003 116: 773-783.
[Abstract]
[Full Text]
