Kashuba Elena, Mattsson Karin, Klein George, Szekely Laszlo
Microbiology and Tumor Biology Center (MTC), Karolinska Institute, S 171 77, Stockholm, Sweden.
Mol Cancer. 2003 Mar 5;2:18. doi: 10.1186/1476-4598-2-18.
p14ARF is a protein product of the alternative reading frame of the human INK4a locus. It functions as a tumor suppressor protein. p14ARF suppresses growth through p53-dependent and p53-independent pathways.
p14ARF protein localizes primarily to the nucleoli. Here we show that in transfected cells p14ARF also appears in Hsp70 positive extranucleolar inclusions. The formation of p14ARF inclusions induces the parallel re-localization p53 and HDM2 to these sites that are also targeted by PML bodies and proteasomes.
Our data show that co-localization between p53, HDM2 and p14ARF occurs at extranucleolar sites. Accumulation of PML and proteasomes at these sites suggest that the components of the nuclear inclusions are targeted for proteasome-mediated degradation.
p14ARF是人类INK4a基因座可变阅读框的蛋白质产物。它作为一种肿瘤抑制蛋白发挥作用。p14ARF通过p53依赖性和p53非依赖性途径抑制生长。
p14ARF蛋白主要定位于核仁。在此我们表明，在转染细胞中，p14ARF也出现在Hsp70阳性的核仁外包涵体中。p14ARF包涵体的形成诱导p53和HDM2平行重新定位于这些也是PML小体和蛋白酶体靶向的位点。
我们的数据表明，p53、HDM2和p14ARF之间的共定位发生在核仁外位点。PML和蛋白酶体在这些位点的积累表明核包涵体的成分被靶向进行蛋白酶体介导的降解。
Zotero 插件
