Regulation of the localisation and function of the oncogene LYRIC/AEG-1 by ubiquitination at K486 and K491.
Regulation of the localisation and function of the oncogene LYRIC/AEG-1 by ubiquitination at K486 and K491.
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DOI：
10.1016/j.molonc.2014.01.009
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发表时间：
2014-05
影响因子：
6.6
通讯作者：
Whitaker HC
中科院分区：
文献类型：
--
作者：
Luxton HJ;Barnouin K;Kelly G;Hanrahan S;Totty N;Neal DE;Whitaker HC
LYRIC/AEG-1在恶性转化、肿瘤发生和化疗耐药性中的关键作用先前已在不同细胞类型和亚细胞区室中得到证实。LYRIC/AEG-1的定位似乎对其功能至关重要，并受三个富含赖氨酸的核定位信号区的调节，其中一个先前被证明是由泛素修饰的。在这里，我们发现LYRIC/AEG-1在K486和K491处的突变导致泛素化的丧失。不能泛素化的K486/491 R双突变体显示与NFκB亚基p65或importin-β的结合减少，导致LYRIC/AEG-1独特的胞核定位。我们还提供了证据表明，TOPORS，一种也调节p53修饰的E3连接酶，可能是LYRIC/AEG-1泛素修饰的原因。总体而言，我们证明了LYRIC/AEG-1泛素化的特定位点对于调节LYRIC/AEG-1定位和功能相互作用蛋白是必不可少的。LYRIC/AEG-1是一种重要的癌基因。exNLS-2中的2个特异性赖氨酸残基被泛素化。两个赖氨酸残基的缺失改变了定位和与p65的相互作用。LYRIC/AEG-1与TOPORS（一种已知的E3连接酶）相互作用。
The pivotal role of LYRIC/AEG‐1 in malignant transformation, tumourigenesis and chemo‐resistance has previously been demonstrated in different cell types and sub‐cellular compartments. The localisation of LYRIC/AEG‐1 appears crucial to its function and is regulated by three lysine‐rich nuclear localisation signal regions, one of which was previously demonstrated to be modified by ubiquitin. Here we show that mutation of LYRIC/AEG‐1 at K486 and K491 results in a loss of ubiquitination. A K486/491R double mutant that is incapable of ubiquitination shows reduced binding to the NFκB subunit p65 or importin‐β resulting in a distinctive peri‐nuclear localisation of LYRIC/AEG‐1. We also provide evidence to suggest that TOPORS, an E3 ligase that also regulates p53 modification may be responsible for LYRIC/AEG‐1 ubiquitin modification. Overall we demonstrate that specific sites of LYRIC/AEG‐1 ubiquitination are essential for regulating LYRIC/AEG‐1 localisation and functionally interacting proteins. LYRIC/AEG‐1 is an important oncogene. 2 specific lysine residues in exNLS‐2 are ubiquitinated. Deletion of both lysine residues changes localisation and interaction with p65. LYRIC/AEG‐1 interacts with TOPORS, a known E3 ligase.
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影响因子：
50.3
作者：
Hu G;Chong RA;Yang Q;Wei Y;Blanco MA;Li F;Reiss M;Au JL;Haffty BG;Kang Y
通讯作者：
Kang Y
影响因子：
4.8
作者：
Rajendra, R;Malegaonkar, D;Rubin, EH
通讯作者：
Rubin, EH
影响因子：
3.4
作者：
Jiang, Tao;Zhu, Anlong;Piao, Daxun
通讯作者：
Piao, Daxun
星形胶质细胞升高基因 1 通过抑制转录因子 FOXO1 促进乳腺癌增殖
影响因子：
8
作者：
Li, J.;Yang, L.;Li, M.
通讯作者：
Li, M.
DOI：
10.1073/pnas.0910936106
发表时间：
2009-12-15
影响因子：
11.1
作者：
Emdad, Luni;Lee, Seok-Geun;Fisher, Paul B.
通讯作者：
Fisher, Paul B.