Blockade of ubiquitin-conjugating enzyme CDC34 enhances anti-myeloma activity of Bortezomib/Proteasome inhibitor PS-341

Dharminder Chauhan, Guilan Li, Teru Hideshima, Klaus Podar, Reshma Shringarpure, Constantine Mitsiades, Nikhil Munshi, P. Renee Yew, Kenneth C. Anderson

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The ubiquitin-conjugating enzyme CDC34 (UBC3) is linked to cell cycle progression in diverse cell types; however, its role in multiple myeloma (MM) pathogenesis is unclear. Here, we show that CDC34 is highly expressed in patient MM cells and MM cell lines versus normal cells. Blocking CDC34 using a dominant-negative strategy enhances the anti-MM activity of Bortezomib/ Proteasome inhibitor PS-341, dexamethasone (Dex) and 2-Methoxyestradiol (2ME2). The expression of wild-type CDC34 reduces Bex-induced cytotoxicity in MM cells. Moreover, inhibition of CDC34 enzymatic activity abrogates interleukin-6-induced protection against Dex-induced apoptosis. Together, these findings provide evidence that (1) CDC34 expression is associated with growth and survival of MM cells and (2) blocking CDC34 activity not only enhances anti-MM activity of Bortezomib and 2ME2 but also overcomes IL-6-triggered Dex-resistance.

Original languageEnglish (US)
Pages (from-to)3597-3602
Number of pages6
JournalOncogene
Volume23
Issue number20
DOIs
StatePublished - Apr 29 2004

Keywords

  • 2-Methoxyestradiol
  • Apoptosis
  • Bortezomib/PS-341
  • Dexamethasone
  • Multiple myeloma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Chauhan, D., Li, G., Hideshima, T., Podar, K., Shringarpure, R., Mitsiades, C., Munshi, N., Yew, P. R., & Anderson, K. C. (2004). Blockade of ubiquitin-conjugating enzyme CDC34 enhances anti-myeloma activity of Bortezomib/Proteasome inhibitor PS-341. Oncogene, 23(20), 3597-3602. https://doi.org/10.1038/sj.onc.1207458