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Title 

Critical role of XBP1 in cancer signalling is regulated by PIN1

Authors 

U ChaeS J ParkB KimS WeiJu-Sik MinJ H LeeS H ParkA H LeeK P LuD S LeeS H Min

Publisher 

Portland Press

Issue Date 

2016

Citation 

Biochemical Journal

Keywords 

CancerIsomerasePIN1XBP1

Abstract 

XBP1 (X-box-binding protein 1) is activated in cancer and has a pivotal role in tumorigenesis and progression of human cancer. In particular, the XBP1 transcriptional regulatory network is well known to drive cancer development, but little is known about whether the stability of XBP1 is regulated and, if so, what controls the stability of XBP1. In the present study we show that PIN1 prolyl isomerase interacts with the active form of XBP1 (XBP1s) in a phosphorylation-dependent manner and promotes XBP1s-induced cell proliferation and transformation through the regulation of XBP1 stability. By contrast, depletion of Pin1 in cancer cells reduced XBP1s expression, which subsequently inhibits cell proliferation and transformation. Interestingly, XBP1s activates multiple oncogenic pathways including NF-κB (nuclear factor κB),AP1 (activator protein 1) and Myc, and downregulates PIN1 transcription via a negative-feedback mechanism through p53 induction. Ultimately, reciprocal regulation of Pin1 and XBP1s is associated with the activation of oncogenic pathways, and the relationship of PIN1 and XBP1 may be an attractive target for novel therapy in cancers.

ISSN 

0264-6021

Link 

http://dx.doi.org/10.1042/BCJ20160482

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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