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

AUTOR(ES)

Liu, Baoying

FONTE

National Academy of Sciences

RESUMO

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 (APCCdc20), 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 APCCdc20 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.

Documentos Relacionados

• Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex
• Degradation of the kinesin Kip1p at anaphase onset is mediated by the anaphase-promoting complex and Cdc20p
• Anaphase-Promoting Complex in Caenorhabditis elegans
• The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation
• Mitotic regulation of the human anaphase-promoting complex by phosphorylation