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增殖细胞核抗原相关因子KIAA0101/p15(PAF)与潜在的肿瘤抑制产物p33ING1b结合。

The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b.

作者信息

Simpson Fiona, Lammerts van Bueren Kelly, Butterfield Natalie, Bennetts Jennifer S, Bowles Josephine, Adolphe Christelle, Simms Lisa A, Young Joanne, Walsh Michael D, Leggett Barbara, Fowles Lindsay F, Wicking Carol

机构信息

Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.

出版信息

Exp Cell Res. 2006 Jan 1;312(1):73-85. doi: 10.1016/j.yexcr.2005.09.020. Epub 2005 Nov 8.

Abstract

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.

摘要

KIAA0101/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)结合伴侣时分离得到的,结果表明它能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。利用针对p15(PAF)融合蛋白产生的多克隆抗血清,我们发现,在一系列哺乳动物肿瘤细胞系和非肿瘤细胞系中,内源性p15(PAF)蛋白定位于细胞核和线粒体。在正常情况下,未检测到与PCNA的共定位,但在紫外线照射后,有可能从多个细胞系中共免疫沉淀p15(PAF)和PCNA,这表明两种蛋白在紫外线照射后关联性增强。还发现,在哺乳动物细胞中过表达p15(PAF)可保护细胞免受紫外线诱导的细胞死亡。基于p15(PAF)与潜在肿瘤抑制产物p33INGlb行为的相似性,我们进一步证明,在细胞培养中这两种蛋白在同一复合物中相互作用。这表明p15(PAF)是一个更大的蛋白复合物的一部分,可能参与DNA修复、细胞凋亡和细胞周期进程的调控。

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