Nat Commun: Phosphate status: RNF43's anti-cancer switch.

Multiple signal path paths that regulate the fate of cells are essential for the normal development of individuals and their own steady state.
Wnt signaling path path is crucial in stem cell maintenance, embryonic development, and tumor development.
the activity of the key factors of the path is regulated by post-translation modifications such as phosphorylation and ubibinization.
these regulatory mechanisms or lead to cancer.
previous studies have shown that mutations in the anti-cancer gene RNF43 are often detected in many cancers, especially colon cancer.
RNF43 is an E3 ubiquity connective enzyme that negatively regulates the Wnt signal transducting path by inducing degradation of Frizzled (curly protein, Wnt signal path pathlineor protein).
the study found that phosphateization of the RNF43 conservative serine triplet was necessary for the protein's active state.
model animal studies have shown that this phosphate state is essential for zebrafish development and the growth of intestinal organs in mice.
mutant RNF43 and active Ras-promoted tumors researchers found that RNF43 cancer-related mutations cause the protein to be in a non-phosphate state, rather than phosphate RNF43 can work with active Ras to promote tumor development.
this effect is mainly achieved by removing the inhibition of RNF43 to the Wnt signal path, while maintaining its inhibition of the p53 signal path.
further studies of the anti-cancer effects of the simulated phosphate recovery mutation RNF43 show that in colon cancer, simultaneous mutations of RNF43 and KRAS can promote multi-step tumor occurrence by mediating the Wnt-Ras-p53 path.
phosphorylation of the parasine triplet can restore tumor inhibition activity of the carcinogenic RNF43 mutants mentioned above.
in general, phosphorylation modification targeting RNF43 may be a potential treatment strategy for RNF43 mutant tumors.
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