RBBP6 Interacts with Multifunctional Protein YB-1 through Its RING Finger Domain, Leading to Ubiquitination and Proteosomal Degradation of YB-1
RBBP6 Interacts with Multifunctional Protein YB-1 through Its RING Finger Domain, Leading to Ubiquitination and Proteosomal Degradation of YB-1
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DOI：
10.1016/j.jmb.2008.09.060
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发表时间：
2008-12-26
影响因子：
5.6
通讯作者：
Pugh, David J. R.
中科院分区：
文献类型：
--
作者：
Chibi, Moredreck;Meyer, Mervin;Pugh, David J. R.
RBBP6（视网膜母细胞瘤结合蛋白6）是一种250 kDa的多功能蛋白，与p53和pRb相互作用，并参与mRNA加工。由于存在RING指结构域，它也被鉴定为推定的E3泛素连接酶，尽管迄今为止还没有鉴定出底物。在酵母双杂交筛选中使用RING指结构域作为诱饵，我们将YB-1（Y-box binding protein 1）鉴定为RBBP6的结合伴侣，将相互作用定位于YB-1的最后62个残基。此外，我们发现全长RBBP6和分离的RING指结构域都能够泛素化YB-1，导致其在蛋白体中降解。结果，RBBP 6能够抑制体内YB-1的水平并降低其反式激活能力。鉴于YB-1在肿瘤发生中的重要作用，我们的研究结果表明RBBP6可能是旨在改变YB-1活性的治疗药物的相关靶点。(C)2008爱思唯尔有限公司保留所有权利。
RBBP6 (retinoblastoma binding protein 6) is a 250-kDa multifunctional protein that interacts with both p53 and pRb and has been implicated in mRNA processing. It has also been identified as a putative E3 ubiquitin ligase due to the presence of a RING finger domain, although no substrate has been identified up to now. Using the RING finger domain as bait in a yeast two-hybrid screen, we identified YB-1 (Y-box binding protein 1) as a binding partner of RBBP6, localising the interaction to the last 62 residues of YB-1. We showed, furthermore, that both full-length RBBP6 and the isolated RING finger domain were able to ubiquitinate YB-1, resulting in its degradation in the proteosome. As a result, RBBP6 was able to suppress the levels of YB-1 ill vivo and to reduce its transactivational ability. In the light of the important role that YB-1 appears to play in tumourigenesis, our results suggest that RBBP6 may be a relevant target for therapeutic drugs aimed at modifying the activity of YB-1.(C) 2008 Elsevier Ltd. All rights reserved.