Axin Ubigenization degradation, which relies on SIHA, is a powerful speed limit step for maintaining the Wnt/beta-catenin signal.

On June 1st, the journal Genes and Development published in its cover paper the latest research on the degradation mechanism of the Wnt signaling path ubiquitin ligases promote Wnt/2-catenin-signaling center, by Liang Dongxuan of the Institute of Biophysics of the Chinese Academy of Sciences and Feng Cong, a professor at the University of Washington.
Wnt/beta-catenin signaling path is playing a vital role in the physiological processes of early embryo development, organ formation and tissue regeneration.
-catenin is the main effect molecule in the Wwnt signaling path, and ensuring the normal degradation of beta-catenin in excess free state in cytoste is the key to maintaining cell stability.
accumulation of free-state beta-catenin causes overactivity of the Wnt/beta-catenin signaling path, leading to tumor formation and metastasis and deterioration of cancer cells.
AXIN is a stent protein in the classical Wnt/beta-catenin signal degradation pathway, which binds to GSK3 beta, CKI, and APC to form a beta-catenin degradation complex.
long-term studies have shown that Axin protein concentration is a key speed limiting factor for beta-catenin degradation complex assembly.
therefore, it is important to study the molecular and physiological events that cause Axin degradation by Wwnt activation to effectively control the infinite amplification of the Wwnt/beta-catenin signal.
study, Liang Dongsi and his collaborators found that E3 Ubigen lysoenase SIAH can mediat the degradation of Axin in the Wwnt signaling path.
studies show that SIAH and GSK3 are competitively combined with Axin, and the VXP base sequence of the GSK3 binding region on SIAH interacts to degrade the Protease pathway after Axin ubiquitinization.
combined with in-cell knockout, molecular dynamics, and 3D structural studies, the researchers revealed that Axin Ubigenization degradation, which relies on SIHA, is a powerful speed-limiting step to maintain the Wnt/beta-catenin signal.
the discovery of Axin degradation mode mediated by SIAH provides a new way to study how to regulate the Wwnt signal path and maintain cell stability.
Jiang Bo of the Institute of Biophysics is the paper's senior author, and associate researcher Yan Xiaoxuan is the paper's co-author.
the study was funded by the National Natural Science Foundation of China (project number: 31570794, 31629002) and the Special Project of Strategic Pilot B Science and Technology of the Chinese Academy of Sciences, and the Protein Research Platform of the Biophysical Institute and the Shanghai Synchrogenic Radiation Light Source provided important technical support for the research.
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