1. Academic Validation
  2. Monoubiquitination of Cancer Stem Cell Marker CD133 at Lysine 848 Regulates Its Secretion and Promotes Cell Migration

Monoubiquitination of Cancer Stem Cell Marker CD133 at Lysine 848 Regulates Its Secretion and Promotes Cell Migration

  • Mol Cell Biol. 2018 Jul 16;38(15):e00024-18. doi: 10.1128/MCB.00024-18.
Fan Yang 1 Yang Xing 1 Yinan Li 1 Xiaoning Chen 1 Jianhai Jiang 1 Zhilong Ai 2 Yuanyan Wei 3
Affiliations

Affiliations

  • 1 Key Laboratory of Glycoconjugate Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.
  • 2 Division of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China ai.zhilong@zs-hospital.sh.cn yywei@fudan.edu.cn.
  • 3 Key Laboratory of Glycoconjugate Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China ai.zhilong@zs-hospital.sh.cn yywei@fudan.edu.cn.
Abstract

CD133, a widely known marker of Cancer Stem Cells, was recently found in extracellular vesicles. However, the mechanisms underlying CD133 translocation to the extracellular space remain largely unknown. Here we report that CD133 is monoubiquitinated. Ubiquitination occurs primarily on complex glycosylated CD133. The lysine 848 residue at the intracellular carboxyl terminus is one of the sites for CD133 ubiquitination. The K848R mutation does not affect CD133 degradation by the lysosomal pathway but significantly reduces CD133 secretion by inhibiting the interaction between CD133 and tumor susceptibility gene 101 (Tsg101). Furthermore, knockdown of the E3 ubiquitin protein Ligase Nedd4 largely impairs CD133 ubiquitination and vesicle secretion. Importantly, CD133-containing vesicles are taken up by recipient cells, consequently promoting cell migration. The K848R mutation reduces cell migration induced by CD133. Taken together, our findings show that monoubiquitination contributes to CD133 vesicle secretion and promotes recipient cell migration. These findings provide a clue to the mechanisms of CD133 secretion and Cancer stem cell microenvironment interactional effects.

Keywords

CD133; Tsg101; cell migration; extracellular vesicles; glycosylation; ubiquitination.

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