FBXW8-dependent degradation of MRFAP1 in anaphase controls mitotic cell death

Duan Zhuo Li, Shun Fang Liu, Lan Zhu, Yu Xing Wang, Yi Xiang Chen, Jie Liu, Gang Hu, Xin Yu, Jian Li, Jin Zhang, Zhi Xiang Wu, Han Lu, Wei Liu, Bin Liu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 downregulated 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 halflife 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.

Original languageEnglish (US)
Pages (from-to)97178-97186
Number of pages9
JournalOncotarget
Volume8
Issue number57
DOIs
StatePublished - 2017

Fingerprint

Telophase
Anaphase
Genomic Instability
Cell Death
Histone Code
F-Box Proteins
Histone Acetyltransferases
Acetyltransferases
Ubiquitin-Protein Ligases
Nucleosomes
Metaphase
Ligases
Nuclear Proteins
Ubiquitin
HeLa Cells
Immunoprecipitation
Proteomics
Chromatin
Half-Life
Proteins

Keywords

  • FBXW8
  • Genomic instability
  • Mitosis
  • MRFAP1

ASJC Scopus subject areas

  • Oncology

Cite this

Li, D. Z., Liu, S. F., Zhu, L., Wang, Y. X., Chen, Y. X., Liu, J., ... Liu, B. (2017). FBXW8-dependent degradation of MRFAP1 in anaphase controls mitotic cell death. Oncotarget, 8(57), 97178-97186. https://doi.org/10.18632/oncotarget.21843

FBXW8-dependent degradation of MRFAP1 in anaphase controls mitotic cell death. / Li, Duan Zhuo; Liu, Shun Fang; Zhu, Lan; Wang, Yu Xing; Chen, Yi Xiang; Liu, Jie; Hu, Gang; Yu, Xin; Li, Jian; Zhang, Jin; Wu, Zhi Xiang; Lu, Han; Liu, Wei; Liu, Bin.

In: Oncotarget, Vol. 8, No. 57, 2017, p. 97178-97186.

Research output: Contribution to journalArticle

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 2017, 'FBXW8-dependent degradation of MRFAP1 in anaphase controls mitotic cell death', Oncotarget, vol. 8, no. 57, pp. 97178-97186. https://doi.org/10.18632/oncotarget.21843
Li, Duan Zhuo ; Liu, Shun Fang ; Zhu, Lan ; Wang, Yu Xing ; Chen, Yi Xiang ; Liu, Jie ; Hu, Gang ; Yu, Xin ; Li, Jian ; Zhang, Jin ; Wu, Zhi Xiang ; Lu, Han ; Liu, Wei ; Liu, Bin. / FBXW8-dependent degradation of MRFAP1 in anaphase controls mitotic cell death. In: Oncotarget. 2017 ; Vol. 8, No. 57. pp. 97178-97186.
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AU - Hu, Gang

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