FBXL8 Stabilizes IκBα and Negatively Regulated NF-κB Activation to Suppress Pancreatic Cancer Progression

International Journal of Biological Sciences 2026 Open access

Read full text
Authors: Chunming Li, Kui Fu, Feifan Wu, Zhihao Fan, Yongpeng Gu, Chaohua Zhang, Qin Lang, Zhu Zhu, Xiong Ding, Jianping Gong, Junhua Gong, Junhua Gong
+1 more Junhua Gong
DOI: 10.7150/ijbs.122689
Cited by: 2

Abstract

. Mechanistically, FBXL8 binds to dephosphorylated IκBα (S32/S36) and mediates K63-linked polyubiquitination at the K38 site of IκBα, thereby stabilizing IκBα and inhibiting NF-κB p65 nuclear translocation. Meanwhile, p65 upregulates the transcription factor YY1, which transcriptionally represses FBXL8 expression, thereby forming a FBXL8-NF-κB feedforward regulatory loop. In conclusion, this study reveals that FBXL8 suppresses PC progression by stabilizing IκBα through non-degradative ubiquitination, and its downregulation via the NF-κB-YY1 axis promotes oncogenic progression. The FBXL8-IκBα-NF-κB pathway represents a promising novel therapeutic target for PC.

Fields of Study & Subjects

NF-κB Signaling Pathways Ubiquitin and proteasome pathways Cell death mechanisms and regulation

Publication details

Journal / source
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Volume
22
Issue
3
Pages
1461–1479
Publication date
8 January 2026
Language
EN