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E3-ligase Skp2 regulates β-catenin expression and maintains hematopoietic stem cell homing.

Authors
  • Wang, Jing1
  • Han, Fei2
  • Lee, Szu-Wei2
  • Wu, Juan1
  • Chan, Chia-Hsin3
  • Zhang, Xian2
  • Gao, Yuan2
  • Su, Hong-Kai4
  • Feng, Zi-Zhen1
  • Xu, Da-Zhi1
  • Lin, Hui-Kuan5
  • 1 State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, China; Department of Molecular and Cellular Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA. , (China)
  • 2 Department of Molecular and Cellular Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
  • 3 Department of Molecular and Cellular Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.
  • 4 State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, China. , (China)
  • 5 Department of Molecular and Cellular Oncology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA; Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 404, Taiwan. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier
Publication Date
Mar 14, 2014
Volume
445
Issue
3
Pages
566–571
Identifiers
DOI: 10.1016/j.bbrc.2014.02.042
PMID: 24561244
Source
Medline
Keywords
License
Unknown

Abstract

The homing ability of hematopoietic stem cells (HSCs) was a critical step for transplantation and subsequent hematopoiesis. Although the HSC transplantation was widely used for many diseases, the mechanism by which HSC homing was regulated remained poorly understood. F-box protein S-phase kinase associated protein2 (Skp2), a component of the Skp2-SCF E3 ligase complex, was regarded as a cell cycle regulator by controlling the level of p21 and p27 through ubiquitination. We recently reported an important role of Skp2 in maintaining HSC pool size, quiescent stage and self-renewal ability. In this current study, we showed that Skp2 was a novel and critical regulator for maintaining the homing of HSCs as well as their residence in the endosteal niche. Microarray analysis together with biochemical validations revealed that Skp2 deficiency profoundly reduced the expression of β-catenin and its target genes. Knockdown of β-catenin mimicked the decline of HSC homing upon Skp2 deficiency, suggesting that Skp2 may regulate β-catenin and its target gene expression to orchestrate HSC homing. Our study not only identified Skp2 as a new regulator for maintaining β-catenin expression and HSC homing, but also suggested that Skp2 may serve as a predictive marker for monitoring the transplantation efficiency.

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