HTLV-1 Tax Effects on Cellular Mitotic Regulation
Uniformed Services University Of The Health Sciences Bethesda United States
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The human T-cell leukemia virus 1 HTLV-1 encodes the tax gene transactivator encoded by the pX region which is a potent activator of viral transcription and Nuclear Factor kappa B NF-kB. Recent data indicate that Tax protein activates the anaphase promoting complexcyclosome APC ahead of schedule, thereby causing the premature degradation of cyclin A, cyclin B1, securin, and Skp2. The premature loss of these mitotic regulators is accompanied by mitotic aberrations and leads to rapid senescence and cell cycle arrest in HeLa and S. cerevisiae cells. This tax-induced rapid senescence tax-IRS of HeLa cells is mediated primarily through a dramatic stabilization of p27KIP, as deficiencies in p27KIP prevent Tax-IRS. Since p27KIP stabilization is accompanied by a surge in the level ofp21CIP1WAF1, this cyclin-dependent kinase inhibitor may also play a role in tax-IRS.