Cross-talk between BubR1 expression and the commitment to differentiate in adipose-derived mesenchymal stem cells.
BubR1 mitotic checkpoint kinase monitors attachment of microtubules to kinetochores and links regulation of the chromosome-spindle attachment to mitotic checkpoint signaling. Defects in BubR1-mediated signaling severely perturb checkpoint control and are linked to diseases such as cancer. Studies using BubR1 mouse models suggest that BubR1 activities prevent premature aging and infertility. In this study, we show that BubR1 depletion in human adipose-derived mesenchymal stem cells (ASCs) precedes loss of the differentiation potential and induction of replicative senescence. These effects occur independently of p16(INK4A) expression and may involve DNA methylation. Our results reveal a new and unsuspected feature of BubR1 expression in regulation of adult stem cell differentiation.
Lee
Janet
J
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Lee
Chang Geun
CG
Lee
Kyo-Won
KW
Lee
Chang-Woo
CW
D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D016922:Cellular Senescence; D019175:DNA Methylation; D005786:Gene Expression Regulation; D019942:Genes, p16; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
C584278:Bub1b protein, mouse; D018797:Cell Cycle Proteins; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases