X-box binding protein 1 (XBP1) is activated in cancer and has a pivotal role in tumorigenesis and progression of human cancer. Especially, the XBP1 transcriptional regulatory network is well known to drive cancer development, but little is known if the stability of XBP1 is regulated and if so, what controls the stability of XBP1. Here 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-kB, AP1 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.
- ©2016 The Author(s)
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