本研究中,通过检测killin在其它p53下游相关基因缺失的情况下能否激活细胞凋亡,证明了p53通过killin介导的S期抑制以及细胞凋亡与p21、puma和bax通路没有直接关系.另外通过将EGFP-PCNA和RFP-killin表达质粒共同转染到cosE5细胞中,并观察细胞处于不同时期时Killin蛋白的分布情况,发现在细胞S期中Killin与PCNA的核定位呈现相互排斥的点状分布,与先前BrdU标记结果吻合.这一结果再次印证了Killin在S期可能抑制DNA复制.同时Killin被观察到在非S期时聚集于核仁内,从而可能影响核糖体RNA的合成.这些发现意味着killin作为主要的p53靶基因之一,可能在细胞周期不同检查点进行调控.
Killinfunctions in p53-mediated S phase arrest and apoptosis in the absence of p21,pumaand bax were reported.Through co-transfection of EGFP-PCNA and RFP-killin plasmids into cosE5 cells,It was shown that Killin and PCNA exhibit in mutually exclusive pattern in the nucleus during S phase.Consistent with previous finding using BrdU labeling,these results confirm that Killin may function in S-phase checkpoint control.Surprisingly,we also observe that Killin localizes mostly in cell nucleolus in non-S phase cells,suggesting apotential role of Killin in negative regulation of rRNA biogenesis.Thus,as a major p53 target gene,killin may mediate p53 functions in multiple cell cycle checkpoints.