LYRIC/AEG-1 overexpression modulates BCCIPα protein levels in prostate tumor cells
LYRIC/AEG-1 overexpression modulates BCCIPα protein levels in prostate tumor cells
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DOI：
10.1016/j.bbrc.2008.04.084
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发表时间：
2008-06-27
影响因子：
3.1
通讯作者：
Britt, D. E.
中科院分区：
文献类型：
--
作者：
Ash, S. C.;Yang, D. Q.;Britt, D. E.
LYRIC/AEG-1是一种独特的蛋白质，已显示其通过激活转录因子NF-κ B促进肿瘤细胞迁移和侵袭。我们进行酵母双杂交筛选，以检测LYRIC/AEG-1相关蛋白，并确定BCCIP，CDKN 1A和BRCA 2相关蛋白参与细胞周期调控和DNA修复。在这里，我们证明了哺乳动物细胞中LYRIC/AEG-1和BCCIP之间的关联，并定义了相互作用的区域。两种蛋白的共表达导致BCCIP α水平降低，蛋白酶体抑制部分消除了这种作用。缺乏相互作用区域的截短的LYRIC/AEG-1构建体不改变BCCIP α蛋白水平。巧合的是，观察到BCCIPa在DUI 45前列腺肿瘤细胞中的过表达诱导了明显的神经内分泌分化。总之，我们的数据表明LYRIC/AEG-1是BCCIP α的负调节因子，通过直接相互作用或潜在地通过涉及NF-κ B信号通路下游效应的间接机制促进蛋白酶体降解。(C)2008年爱思唯尔公司All rights reserved.
LYRIC/AEG-1 is a unique protein that has been shown to promote tumor cell migration and invasion through activation of the transcription factor NF-kappa B. We performed yeast two-hybrid screening to detect LYRIC/AEG-1 associated proteins, and identified BCCIP, a CDKN1A and BRCA2-associated protein involved in cell cycle regulation and DNA repair. Here, we demonstrate association between LYRIC/AEG-1 and BCCIP in mammalian cells, and define the region of interaction. Co-expression of the two proteins resulted in decreased levels of BCCIP alpha, an effect partially abrogated by proteasome inhibition. A truncated LYRIC/AEG-1 construct lacking the interaction region did not alter BCCIP alpha protein levels. Coincidentally, it was observed that overexpression of BCCIPa in DUI 45 prostate tumor cells induced an apparent neuroendocrine differentiation. In summary, our data suggest LYRIC/AEG-1 is a negative regulator of BCCIP alpha, promoting proteasomal degradation either through direct interaction, or potentially through an indirect mechanism involving downstream effects of the NF-kappa B signaling pathway. (C) 2008 Elsevier Inc. All rights reserved.