Von Hippel-Lindau gene product directs cytokinesis: a new tumor suppressor function
- Authors
- Sinha, Sutapa; Mondal, Gourish; Hwang, Eun Ju; Han, Da Woon; Dutta, Shamit K.; Iyer, Seethalakshmi; Karumanchi, S. Ananth; Kim, Keun Il; Couch, Fergus J.; Mukhopadhyay, Debabrata
- Issue Date
- Jul-2011
- Publisher
- COMPANY BIOLOGISTS LTD
- Keywords
- pVHL; CIN; SUMOylation; Cytokinesis; Alix; Endobrevin
- Citation
- JOURNAL OF CELL SCIENCE, v.124, no.13, pp 2132 - 2142
- Pages
- 11
- Journal Title
- JOURNAL OF CELL SCIENCE
- Volume
- 124
- Number
- 13
- Start Page
- 2132
- End Page
- 2142
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/12538
- DOI
- 10.1242/jcs.087122
- ISSN
- 0021-9533
1477-9137
- Abstract
- One of the mechanisms of tumorigenesis is that the failure of cell division results in genetically unstable, multinucleated cells. Here we show that pVHL, a tumor suppressor protein that has been implicated in the pathogenesis of renal cell carcinoma (RCC), plays an important role in regulation of cytokinesis. We found that pVHL-deficient RCC 786-O cells were multinucleated and polyploid. Reintroduction of wild-type pVHL into these cells rescued the diploid cell population, whereas the mutant pVHL-K171G failed to do so. We demonstrate that lysine 171 of pVHL is important for the final step of cytokinesis: the midbody abscission. The pVHL-K171G caused failure to localize the ESCRT-1 interacting protein Alix and the v-SNARE complex component Endobrevin to the midbody in 786-O cells, leading to defective cytokinesis. Moreover, SUMOylation of pVHL at lysine 171 might modulate its function as a cytokinesis regulator. pVHL tumor suppressor function was also disrupted by the K171G mutation, as evidenced by the xenograft tumor formation when 786-O clones expressing pVHL-K171G were injected into mice. Most RCC cell lines show a polyploid chromosome complement and consistent heterogeneity in chromosome number. Thus, this study offers a way to explain the chromosome instability in RCC and reveals a new direction for the tumor suppressor function of pVHL, which is independent of its E3 ubiquitin ligase activity.
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