External Homology but Differential Function — Fbxl14A and Fbxl14B
Source:
Time: 2012-04-11
The F-box family of proteins, which are the substrate-recognition components of the Skp1–Cul1–F-box-protein ubiquitin ligase, are important players in a spectrum of pathophysiological processes, such as individual development and tumorigenesis. However, in contrast to the large number of F-box proteins, the functions of many F-box proteins remain elusive. Recently, a team of researchers, led by Prof. LI Yiping, at Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Chinese Academy of Sciences, provided direct evidences that Fbxl14a and Fbxl14b function as essential regulators of dorsoventral patterning in zebrafish embryos. Their data suggested that Fbxl14a and Fbxl14b play distinct functions, although sharing a high sequence homology.
To examine the function of Fbxl14a and Fbxl14b in embryonic development, ZHENG Hongping and his colleagues, under the supervision of Prof. LI Yiping, used combined methods of development, biochemistry, and cell biology, and uncovered the functions of two homologues and the underlying mechanism. Through gain- and loss-of-function experiments, they demonstrate that Fbxl14a is a weak dorsalizing inhibitor, whereas Fbxl14b exhibits dorsalizing activity. Further, they show that their roles in axis formation are executed through modulation of their substrate protein and ubiquitination levels differentially.
This work entitled “Essential role of Fbxl14 ubiquitin ligase in regulation of vertebrate axis formation through modulating Mkp3 level” was published online in Cell Research on March 13th, 2012, before its appearance in print.
This study was supported by grants from the Major State Basic Research Development Program of China and the Shanghai Municipal Commission for Science and Technology.
AUTHOR CONTACT:
LI Yiping
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Shanghai, China
fbxl14b overexpression caused zebrafish embryos to be dorsalized, while in contrast fbxl14a overexpression caused no observable phenotype. (Image provided by Prof. LI Yiping)