The roles of Versican V1 and V2 isoforms in cell proliferation and apoptosis

Wang Sheng, Guizhi Wang, Yelina Wang, Jiyong Liang, Jianping Wen, Peng Sheng Zheng, Yaojiong Wu, Vivian Lee, Joyce M Slingerland, Dan Dumont, Burton B. Yang

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Versican is a large chondroitin sulfate proteoglycan belonging to the lectican family. Alternative splicing of versican generates at least four isoforms named V0, V1, V2, and V3. We have shown that the versican V1 isoform not only enhanced cell proliferation, but also modulated cell cycle progression and protected the cells from apoptosis. Futhermore, the V1 isoform was able to not only activate proto-oncogene EGFR expression and modulate its downstream signaling pathway, but also induce p27 degradation and enhance CDK2 kinase activity. As well, the V1 isoform down-regulated the expression of the proapoptotic protein Bad. By contrast, the V2 isoform exhibited opposite biological activities by inhibiting cell proliferation and down-regulated the expression of EGFR and cyclin A. Furthermore, V2 did not contribute apoptotic resistance to the cells. In light of these results, we are reporting opposite functions for the two versican isoforms whose expression is differentially regulated. Our studies suggest that the roles of these two isoforms are associated with the subdomains CSβ and CSα, respectively. These results were confirmed by silencing the expression of versican V1 with small interfering RNA (siRNA), which abolished V1-enhanced cell proliferation and V1-induced reduction of apoptosis.

Original languageEnglish
Pages (from-to)1330-1340
Number of pages11
JournalMolecular Biology of the Cell
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

Fingerprint

Versicans
Protein Isoforms
Cell Proliferation
Apoptosis
Chondroitin Sulfate Proteoglycans
Cyclin A
Proto-Oncogenes
Alternative Splicing
Small Interfering RNA
Cell Cycle
Phosphotransferases

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Sheng, W., Wang, G., Wang, Y., Liang, J., Wen, J., Zheng, P. S., ... Yang, B. B. (2005). The roles of Versican V1 and V2 isoforms in cell proliferation and apoptosis. Molecular Biology of the Cell, 16(3), 1330-1340. https://doi.org/10.1091/mbc.E04-04-0295

The roles of Versican V1 and V2 isoforms in cell proliferation and apoptosis. / Sheng, Wang; Wang, Guizhi; Wang, Yelina; Liang, Jiyong; Wen, Jianping; Zheng, Peng Sheng; Wu, Yaojiong; Lee, Vivian; Slingerland, Joyce M; Dumont, Dan; Yang, Burton B.

In: Molecular Biology of the Cell, Vol. 16, No. 3, 01.03.2005, p. 1330-1340.

Research output: Contribution to journalArticle

Sheng, W, Wang, G, Wang, Y, Liang, J, Wen, J, Zheng, PS, Wu, Y, Lee, V, Slingerland, JM, Dumont, D & Yang, BB 2005, 'The roles of Versican V1 and V2 isoforms in cell proliferation and apoptosis', Molecular Biology of the Cell, vol. 16, no. 3, pp. 1330-1340. https://doi.org/10.1091/mbc.E04-04-0295
Sheng, Wang ; Wang, Guizhi ; Wang, Yelina ; Liang, Jiyong ; Wen, Jianping ; Zheng, Peng Sheng ; Wu, Yaojiong ; Lee, Vivian ; Slingerland, Joyce M ; Dumont, Dan ; Yang, Burton B. / The roles of Versican V1 and V2 isoforms in cell proliferation and apoptosis. In: Molecular Biology of the Cell. 2005 ; Vol. 16, No. 3. pp. 1330-1340.
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