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Title 

A negative feedback loop between XBP1 and Fbw7 regulates cancer development

Authors 

U ChaeH LeeB KimHaiyoung JungB M KimA H LeeD S LeeS H Min

Publisher 

Nature Publishing Group

Issue Date 

2019

Citation 

Oncogenesis

Abstract 

In cancer, activation of X-box binding protein (XBP1) has a critical role in tumorigenesis and cancer progression. Transcriptional regulatory mechanism of XBP1 in cancer development has been well known, however, regulation of ubiquitination and degradation of XBP1 has not been elucidated yet. Here we show that Fbw7, a substrate recognition component of the SKP1-Cullin-F-box-type E3 ligase, interacts with XBP1 in a phosphorylation-dependent manner, and facilitates XBP1 ubiquitination and protein degradation. Moreover, Fbw7 inhibits oncogenic pathways including NF-κB, AP1, and Myc induced by XBP1. Interestingly, XBP1 negatively regulates transcription of Fbw7 via a feedback mechanism through NF-κB/E2F-1 axis signaling pathway, suggesting that overexpression of XBP1s may contribute to low level of Fbw7 expression in human cancers. Therefore, a negative feedback loop between Fbw7 and XBP1 contributes to the regulation of tumor development and can be an attractive target for novel therapy in cancers.

URI 

https://doi.org/10.1038/s41389-019-0124-4

ISSN 

2157-9024

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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