TITLE

Pin1 regulates turnover and subcellular localization of �-catenin by inhibiting its interaction with APC

AUTHOR(S)

Ryo, Akihide; Nakamura, Masafumi; Wulf, Gerburg; Liou, Yih-Cherng; Lu, Kun Ping

PUB. DATE

September 2001

SOURCE

Nature Cell Biology;Sep2001, Vol. 3 Issue 9, p793

SOURCE TYPE

Academic Journal

DOC. TYPE

Article

ABSTRACT

Phosphorylation on a serine or threonine residue preceding proline (Ser/Thr-Pro) is a key regulatory mechanism, and the conformation of certain phosphorylated Ser/Thr-Pro bonds is regulated specifically by the prolyl isomerase Pin1. Whereas the inhibition of Pin1 induces apoptosis, Pin1 is strikingly overexpressed in a subset of human tumours. Here we show that Pin1 regulates �-catenin turnover and subcellular localization by interfering with its interaction with adenomatous polyposis coli protein (APC). A differential-display screen reveals that Pin1 increases the transcription of several �-catenin target genes, including those encoding cyclin D1 and c-Myc. Manipulation of Pin1 levels affects the stability of �-catenin in vitro. Furthermore, �-catenin levels are decreased in Pin1-deficient mice but are increased and correlated with Pin1 overexpression in human breast cancer. Pin1 directly binds a phosphorylated Ser-Pro motif next to the APC-binding site in �-catenin, inhibits its interaction with APC and increases its translocation into the nucleus. Thus, Pin1 is a novel regulator of �-catenin signalling and its overexpression might contribute to the upregulation of �-catenin in tumours such as breast cancer, in which APC or �-catenin mutations are not common.

ACCESSION #

8783791

Tags: ISOMERASES;  TRANSCRIPTION factors

 

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