TI - Tax stabilizes p27 but does not affect p21 protein turn-over . AB - We have shown recently that the premature activation of the mitotic E3 ubiquitin ligase , the anaphase promoting complex , by Tax leads to the polyubiqutination and degradation of Skp2 , and consequently , inactivation of the G1/S E3 ubiquitin ligase , SCFSkp2 . As a result , p27 , a key SUBstrates of SCFSkp2 , becomes greatly stabilized when Tax is expressed , causing HeLa cells to enter into a state of irreversible G1 arrest termed Tax-induced rapid senescence ( Tax-IRS ) [23] . Based on a previous report that suggested that p21 might be a SUBstrate of SCFSkp2 [44] , we initially attributed the concurrent and even more dramatic surge in p21 induced by Tax to the inactivation of SCFSkp2 . To determine the rate of p21 and p27 protein turnover , HeLa/18 x 21-EGFP cells transduced with LV-Tax or a control lentivirus vector , LV-puro , were treated with cycloheximide to inhibit de novo protein synthesis . The abundance of p21 and p27 in transduced cells was then measured after the cessation of protein translation . As indicated and reported previously [23] , the half-life of p27 in cells transduced by LV-Tax is considerably longer than that in cells transduced with LV-puro (Fig 5A) . A different result was obtained when the half-life of p21 was measured . As shown in Fig. 5B , the stability of p21 is not significantly altered by Tax (Fig 5B) . These results confirm the notion that p27 is a SUBstrate of SCFSkp2 and becomes stabilized as a consequence of premature activation of APC/C and inactivation of SCFSkp2 by Tax . By contrast , even though the Tax -induced increase in p21 and p27 correlated with APC/C activation , the up-regulation of p21 by Tax is achieved by a mechanism independent of SCFSkp2 - and ubiquitin-mediated protein turnover .