期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 1, 页码 63-68出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0406424101
关键词
adult T cell leukemia; cell cycle; ubiquitination; mitosis; chromosome instability
Expression of the human T lymphotropic virus type 1 (HTLV-1) 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-1-transformed T cells progress through S/G(2)/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/G(2). Consistent with the notion that Tax activates ApC(Cdc20) directly, Tax is found to coimmunoprecipitate with Cdc20 and Cdc27/APC3. The ApCCdc20 activity prematurely activated by Tax remains sensitive to spindle checkpoint inhibition. Unscheduled activation of ApC(Cdc20) by Tax provides an explanation for the mitotic abnormalities in HTLV-1-infected cells and is likely to play an important role in the development of adult T cell leukemia.
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