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Phosphorylation-specific prolyl isomerization: is there an underlying theme?

Nature Cell Biology volume 7, pages 435–441 (2005)Cite this article

Abstract

The prolyl isomerase Pin1 is a conserved enzyme that is intimately involved in diverse biological processes and pathological conditions such as cancer and Alzheimer's disease. By catalysing cis–trans interconversion of certain motifs containing phosphorylated serine or threonine residues followed by a proline residue (pSer/Thr-Pro), Pin1 can have profound effects on phosphorylation signalling. The structural and functional differences that result from cis–trans isomerization of specific pSer/Thr-Pro motifs probably underlie most, if not all, Pin1-dependent actions. Phosphorylation-dependent prolyl isomerization by Pin1 remains a unique mode for the modulation of signal transduction. Here, we provide an overview of the plethora of regulatory events that involve this unique enzyme, with a particular focus on oncogenic signalling and neurodegeneration.

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Figure 1: Pin1 functions as a critical catalyst for multiple pro-proliferative and pro-apoptotic pathways.
Figure 2: Models for the effects of Pin1-catalysed prolyl isomerization on its substrates.

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Acknowledgements

Owing to space limitations we could not include all relevant references, for which we apologise. We are grateful to B. Neel, L. Cantley, T. Hunter and to the members of the Lu laboratory for stimulating discussions. K.P.L. is a Pew Scholar and a Leukemia and Lymphoma Society Scholar. Work done in the authors' laboratory is supported by NIH grants Mentored Clinician Scientist Award CA093655 to G. W. and GM56230, GM58556, AG17870 and AG22082 to K.P.L.

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  1. Division of Hematology/Oncology, Department of Medicine, Cancer Biology Program, Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 1030, Boston, 02115, MA, USA

    Gerburg Wulf, Greg Finn, Futoshi Suizu & Kun Ping Lu

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  1. Gerburg Wulf
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Correspondence to Gerburg Wulf or Kun Ping Lu.

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K. P. Lu is a member of the Scientific Advisory Board and a Consultant for Pintex Pharmaceutical, Inc. However, the work described in this review was not supported by Pintex or any other pharmaceutical company.

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Wulf, G., Finn, G., Suizu, F. et al. Phosphorylation-specific prolyl isomerization: is there an underlying theme?. Nat Cell Biol 7, 435–441 (2005). https://doi.org/10.1038/ncb0505-435

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