TRAF6 regulates YAP signaling by promoting the ubiquitination and degradation of MST1 in pancreatic cancer.

Abstract

TNF receptor-associated factor 6 (TRAF6), a regulator of NF-κB signaling, has been reported to be associated with the oncogenesis of various tumors including pancreatic cancer, but the underlying mechanisms remain unknown. Here, we found that knocking down the expression of TRAF6 impaired YAP signaling. Moreover, TRAF6 promoted the migration and colony formation of pancreatic cancer cells through YAP. Then, we found that TRAF6 interacted with and promoted the ubiquitination and degradation of MST1, and the expression of TRAF6 and MST1 was negatively correlated in primary human pancreatic cancer samples. Our results reveal that TRAF6 regulates YAP signaling by promoting the ubiquitination and degradation of MST1 in pancreatic cancer, suggesting that TRAF6 could be a possible E3 ligase of MST1 and a potential therapeutic target.

• Authors: Jian-Ang Li, Tiantao Kuang, Ning Pu, Yuan Fang, Xu Han, Lei Zhang, Xuefeng Xu, Wenchuan Wu, Dansong Wang, Wenhui Lou, Yefei Rong
• Journal: Clinical and experimental medicine (Clin Exp Med) Vol. 19 Issue 2 Pg. 211-218 (May 2019) ISSN: 1591-9528 [Electronic] Italy
• PMID: 30673917 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Intracellular Signaling Peptides and Proteins
• Phosphoproteins
• TNF Receptor-Associated Factor 6
• Tifab protein, human
• Transcription Factors
• YAP-Signaling Proteins
• YAP1 protein, human
• STK4 protein, human
• Protein Serine-Threonine Kinases

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Humans
• Intracellular Signaling Peptides and Proteins
• Pancreatic Neoplasms (pathology)
• Phosphoproteins (metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Proteolysis
• Signal Transduction
• TNF Receptor-Associated Factor 6 (metabolism)
• Transcription Factors
• Ubiquitination
• YAP-Signaling Proteins