TY - JOUR
T1 - HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule
AU - Liu, Baoying
AU - Hong, Sohee
AU - Tang, Zhanyun
AU - Yu, Hongtao
AU - Giam, Chou Zen
PY - 2005/1/4
Y1 - 2005/1/4
N2 - 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.
AB - 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.
KW - Adult T cell leukemia
KW - Cell cycle
KW - Chromosome instability
KW - Mitosis
KW - Ubiquitination
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UR - http://www.scopus.com/inward/citedby.url?scp=11844249376&partnerID=8YFLogxK
U2 - 10.1073/pnas.0406424101
DO - 10.1073/pnas.0406424101
M3 - Article
C2 - 15623561
AN - SCOPUS:11844249376
SN - 0027-8424
VL - 102
SP - 63
EP - 68
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -