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Related Experiment Video

Updated: Jan 28, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
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A negative feedback loop between XBP1 and Fbw7 regulates cancer development.

Unbin Chae1, Heejin Lee1,2, Bokyung Kim1,3

  • 1School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.

Oncogenesis
|February 21, 2019
PubMed
Summary

Fbw7 targets X-box binding protein (XBP1) for degradation, inhibiting cancer pathways. A feedback loop between Fbw7 and XBP1 regulates tumor development, offering a potential therapeutic target.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • X-box binding protein (XBP1) activation is crucial for cancer development and progression.
  • While XBP1's transcriptional regulation in cancer is known, its ubiquitination and degradation mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the ubiquitination and degradation pathways of XBP1.
  • To investigate the role of Fbw7 in regulating XBP1 stability and its impact on oncogenic pathways.

Main Methods:

  • Investigated the interaction between Fbw7 and XBP1 using biochemical assays.
  • Assessed the effect of Fbw7 on XBP1 ubiquitination and degradation.
  • Analyzed the impact of Fbw7-mediated XBP1 regulation on NF-κB, AP1, and Myc signaling pathways.
  • Examined the feedback mechanism between XBP1 and Fbw7 transcription.

Main Results:

  • Fbw7 directly interacts with XBP1 in a phosphorylation-dependent manner.
  • Fbw7 facilitates the ubiquitination and subsequent degradation of XBP1.
  • Fbw7 inhibits XBP1-driven oncogenic pathways, including NF-κB, AP1, and Myc.
  • XBP1 negatively regulates Fbw7 transcription through an NF-κB/E2F-1 feedback loop, potentially leading to lower Fbw7 levels in cancers.

Conclusions:

  • A novel negative feedback loop exists between Fbw7 and XBP1, crucial for regulating tumor development.
  • Targeting the Fbw7-XBP1 interaction presents a promising therapeutic strategy for cancer treatment.