The PCNA-associated factor KIAA0101/p15PAF binds the potential tumor suppressor product p33ING1b

The PCNA-associated factor KIAA0101/p15PAF binds the potential tumor suppressor product p33ING1b
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DOI:
10.1016/j.yexcr.2005.09.020
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发表时间:
2006-01-01
影响因子:
3.7
通讯作者:
Wicking, C
Wicking, C
中科院分区:
医学3区
文献类型:
--
作者:
Simpson, F;van Bueren, KL;Wicking, C

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KIAA 0101/p15(PAF)/OEATC-1蛋白最初是在酵母双杂交筛选增殖细胞核抗原(PCNA)结合伴侣中分离出来的,并显示与细胞周期调节因子p21(WAF)竞争性结合PCNA。PCNA参与DNA复制和损伤修复。使用针对p15(PAF)融合蛋白的多克隆抗血清,我们已经表明,在一系列哺乳动物肿瘤和非肿瘤细胞系的内源性p15(PAF)蛋白定位于细胞核和线粒体。在正常条件下,没有共定位与PCNA可以检测到,但是暴露于UV后,它是可能的共免疫沉淀p15(PAF)和PCNA从一些细胞系,这表明一个UV增强协会的两种蛋白质。在哺乳动物细胞中过表达p15(PAF)也被发现保护细胞免受紫外线诱导的细胞死亡。基于p15(PAF)和潜在的肿瘤抑制产物p33 ING 1b之间的行为相似性,我们进一步表明,这两种蛋白质在细胞培养中在同一复合物中相互作用。这表明,p15(PAF)形成一个更大的蛋白质复合物的一部分,可能参与DNA修复,凋亡和细胞周期进程的调节。(c)2005年爱思唯尔公司All rights reserved.
The KIAA0101/p15(PAF)/OEATC-1 protein was initially isolated in a yeast two-hybrid screen for proliferating cell nuclear antigen (PCNA) binding partners, and was shown to bind PCNA competitively with the cell cycle regulator p21(WAF). PCNA is involved in DNA replication and damage repair. Using polyclonal antisera raised against a p15(PAF) fusion protein, we have shown that in a range of mammalian tumor and non-tumor cell lines the endogenous p15(PAF) protein localises to the nucleus and the mitochondria. Under normal conditions no co-localisation with PCNA could be detected, however following exposure to UV it was possible to co-immunoprecipitate p15(PAF) and PCNA from a number of cell lines, suggesting a UV-enhanced association of the two proteins. Overexpression of p15(PAF) in mammalian cells was also found to protect cells from UV-induced cell death. Based on similarities between the behaviour of p15(PAF) and the potential tumor suppressor product p33ING1b, we have further shown that these two proteins interact in the same complex in cell cultures. This suggests that p15(PAF) forms part of a larger protein complex potentially involved in the regulation of DNA repair, apoptosis and cell cycle progression. (c) 2005 Elsevier Inc. All rights reserved.