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FBXW8-dependent degradation of MRFAP1 in anaphase controls mitotic cell death. Oncotarget 2017 Nov 14;8(57):97178-97186



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Pubmed Central ID




Scopus ID

2-s2.0-85033786438 (requires institutional sign-in at Scopus site)   7 Citations


Mof4 family associated protein 1 (MRFAP1) is a 14 kDa nuclear protein, which involves in maintaining normal histone modification levels by negatively regulating recruitment of the NuA4 (nucleosome acetyltransferase of H4) histone acetyltransferase complex to chromatin. MRFAP1 has been identified as one of the most up-regulated proteins after NEDD8 (neural precursor cell expressed developmentally down-regulated 8) inhibition in multiple human cell lines. However, the biological function of MRFAP1 and the E3 ligase that targets MRFAP1 for destruction remain mysterious. Here we show, by using an immunoprecipitation-based proteomics screen, that MRFAP1 is an interactor of the F-box protein FBXW8. MRFAP1 is degraded by means of the ubiquitin ligase Cul7/FBXW8 during mitotic anaphase-telophase transition and accumulated in mitotic metaphase. Overexpression of FBXW8 increased the polyubiquitination and decreased the stability of MRFAP1, whereas knockdown of FBXW8 prolonged the half-life of MRFAP1. Moreover, forced expression of MRFAP1 in HeLa cells caused growth retardation and genomic instability, leading to severe mitotic cell death. Thus, Cul7/FBXW8-mediated destruction of MRFAP1 is a regulatory component monitoring the anaphase-telophase transition and preventing genomic instability.

Author List

Li DZ, Liu SF, Zhu L, Wang YX, Chen YX, Liu J, Hu G, Yu X, Li J, Zhang J, Wu ZX, Lu H, Liu W, Liu B


Wei Liu PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Lan Zhu PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin