On March 13th, Cell Research published online the research results of Li Yiping's research group of the Institute of Biochemistry and Cell Research, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences on "ubiquitin ligase Fbxl14 plays an important role in vertebrate axis development"
Ubiquitin ligase, as a post-translational effector, is essential for the normal operation of cell life activities. The main function of the ubiquitin ligase SCF (Skp1-Cullin-F-box protein) complex is the specific recognition of the target protein. Although studies have reported that some F-box proteins play an important role in the development of organisms and even in the pathogenesis of tumors, the function of most F-box proteins is unclear.
Through research on the expression, function and regulation of multiple F-box genes in zebrafish embryos, Dr. Zheng Hongping, a doctoral student in Li Yiping's research group, discovered that Fbxl14A and its homologous protein Fbxl14B were involved in the development of the zebrafish embryo's dorsal and abdominal axis Played an important function. Fbx114A and Fbx114B have very high homology in amino acid sequence, but their functions are quite different, which is an interesting phenomenon. Fbxl14A is an inhibitor of dorsalization, while Fbxl14B can significantly promote the development of embryos toward dorsalization.
Further research found that Fbxl14B can bind to Mkp3 and promote the latter's ubiquitination degradation. On the contrary, Fbxl14A can reduce the ubiquitination level of Mkp3 and inhibit its degradation. Combined with people's existing understanding of the function of Mkp3, the results of research on the ubiquitination and protein level regulation of Mkp3 clearly revealed the functional mechanism of Fbxl14A / B in the process of embryonic dorsal-ventral axis formation.
Because of the association between Mkp3 and tumors, the results of this research on the mechanism of action of Fbxl14 will help to reveal the mechanism of tumor formation and drug resistance.
The research work was supported by the Ministry of Science and Technology and the Shanghai Science and Technology Commission.
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