HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule

Baoying Liu, Sohee Hong, Zhanyun Tang, Hongtao Yu, Chou Zen Giam

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Expression of the human T lymphotropic virus type I (HTLV-I) transactivator/oncoprotein. Tax, leads to faulty mitosis as reflected by chromosome aneuploidy, cytokinesis failure, and formation of micro- and multinucleated cells. Here we show that HTLV-I-transformed T cells progress through S/G2/M phases of the cell cycle with a delay. This delay is correlated with a decrease in the levels of cyclin A, cyclin B1, and securin. In tax-expressing cells, the Cdc20-associated anaphase promoting complex (APC Cdc20), an E3 ubiquitin ligase that controls metaphase to anaphase transition, becomes active before cellular entry into mitosis as evidenced by premature cyclin B1 polyubiquitination and degradation during S/G2. Consistent with the notion that Tax activates APCCdc20 directly, Tax is found to coimmunoprecipitate with Cdc20 and Cdc27/APC3. The APC Cdc20 activity prematurely activated by Tax remains sensitive to spindle checkpoint inhibition. Unscheduled activation of APCCdc20 by Tax provides an explanation for the mitotic abnormalities in HTLV-I-infected cells and is likely to play an important role in the development of adult T cell leukemia.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number1
DOIs
StatePublished - Jan 4 2005

Keywords

  • Adult T cell leukemia
  • Cell cycle
  • Chromosome instability
  • Mitosis
  • Ubiquitination

ASJC Scopus subject areas

  • General

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