Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity
Authors
Kuo, Tse-ChunChen, Chun-Ting
Baron, Desiree
Onder, Tamer T.
Loewer, Sabine
Almeida, Sandra
Weismann, Cara M.
Xu, Ping
Houghton, JeanMarie
Gao, Fen-Biao
Daley, George Q.
Doxsey, Stephen J.
UMass Chan Affiliations
Department of Medicine, Division of GastroenterologyDepartment of Neurology
Program in Molecular Medicine
Document Type
Journal ArticlePublication Date
2011-09-11Keywords
Animals*Autophagy
Calcium-Binding Proteins
Cell Cycle Proteins
Cell Differentiation
Cell Division
Cell Line
Cell Proliferation
Cell Transformation, Neoplastic
Centrosome
Chromosomal Proteins, Non-Histone
Coculture Techniques
Embryonic Stem Cells
HeLa Cells
Humans
Induced Pluripotent Stem Cells
Lysosomes
Mice
Neoplastic Stem Cells
Nuclear Proteins
*Nuclear Reprogramming
Organelles
Proteins
RNA Interference
Recombinant Fusion Proteins
Time Factors
Transfection
Cellular and Molecular Physiology
Metadata
Show full item recordAbstract
The midbody is a singular organelle formed between daughter cells during cytokinesis and required for their final separation. Midbodies persist in cells long after division as midbody derivatives (MB(d)s), but their fate is unclear. Here we show that MB(d)s are inherited asymmetrically by the daughter cell with the older centrosome. They selectively accumulate in stem cells, induced pluripotent stem cells and potential cancer 'stem cells' in vivo and in vitro. MB(d) loss accompanies stem-cell differentiation, and involves autophagic degradation mediated by binding of the autophagic receptor NBR1 to the midbody protein CEP55. Differentiating cells and normal dividing cells do not accumulate MB(d)s and possess high autophagic activity. Stem cells and cancer cells accumulate MB(d)s by evading autophagosome encapsulation and exhibit low autophagic activity. MB(d) enrichment enhances reprogramming to induced pluripotent stem cells and increases the in vitro tumorigenicity of cancer cells. These results indicate unexpected roles for MB(d)s in stem cells and cancer 'stem cells'.Source
Nat Cell Biol. 2011 Sep 11;13(10):1214-23. doi: 10.1038/ncb2332. Link to article on publisher's siteDOI
10.1038/ncb2332Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37739PubMed ID
21909099Notes
Co-author Tse-Chun Kuo is a student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/ncb2332
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