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Biochem J. 2016 Sep 1;473(17):2603-10. doi: 10.1042/BCJ20160482. Epub 2016 Jun 22.

Critical role of XBP1 in cancer signalling is regulated by PIN1.

Author information

1
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
2
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea Renal Division, School of Medicine, Washington University in St Louis, St. Louis, MO 63130, U.S.A.
3
Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA 02115, U.S.A.
4
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
5
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea New Drug Development Center, DGMIF, Daegu, Republic of Korea.
6
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
7
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, U.S.A.
8
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea shmin03@dgmif.re.k lee1@knu.ac.kr.
9
New Drug Development Center, DGMIF, Daegu, Republic of Korea shmin03@dgmif.re.k lee1@knu.ac.kr.

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 down-regulates 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.

KEYWORDS:

PIN1; XBP1; cancer; isomerase

PMID:
27334111
DOI:
10.1042/BCJ20160482
[Indexed for MEDLINE]

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