Nuclear IRS-1 and cancer.
Nuclear IRS-1 and cancer.
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DOI：
10.1002/jcp.24019
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发表时间：
2012-08
影响因子：
5.6
通讯作者：
Trojanek, Joanna
中科院分区：
文献类型：
--
作者：
Reiss, Krzysztof;Del Valle, Luis;Lassak, Adam;Trojanek, Joanna
胰岛素受体底物家族(IRS)由四种蛋白质(IRS-1-IRS-4)组成，它们最初被认为是参与胰岛素受体(IR)和胰岛素样生长因子I受体(IGF-IR)信号转导的典型胞质接头蛋白。第一个克隆和鉴定的IRS家族成员IRS-1预测其分子量为132 kDa，然而，由于其广泛的丝氨酸磷酸化，它在SDS凝胶上分离出一条约160-185 kDa的条带。IRS-1除了具有促进新陈代谢和促进生长的功能外，还被怀疑在恶性转化中发挥作用。IRS-1支持肿瘤生长的机制尚不完全清楚，IRS-1只是放大IGF-1R和/或IR信号的论点需要进一步研究。近十年前，我们报道了髓母细胞瘤临床标本中存在核IRS-1，表达病毒癌蛋白，人类多瘤病毒JC的大T抗原(JCV T抗原)。核IRS-1的第一次演示在其他几个实验室得到了证实。在IGF-I刺激的永生化成纤维细胞、肝细胞、32D细胞和骨肉瘤细胞系中，表达SV40T抗原v-Src的细胞也检测到核IRS-1。最近，在雌激素受体α(ERα)相关的乳腺癌细胞和表达ERβ的JC病毒阴性的髓母细胞瘤细胞中检测到核IRS-1，进一步表明核IRS-1参与了细胞转化。在这里，我们讨论了核IRS-1如何作用于DNA修复的保真度、转录活性和细胞生长，以支持肿瘤的发展和进展。
The family of insulin receptor substrates (IRS) consists of four proteins (IRS-1 - IRS-4), which were initially characterized as typical cytosolic adaptor proteins involved in insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) signaling. The first cloned and characterized member of the IRS family, IRS-1, has predicted molecular weight of 132 kDa, however, as a result of its extensive serine phosphorylation it separates on a SDS gel as a band of approximately 160–185 kDa. In addition to its metabolic and growth-promoting functions, IRS-1 is also suspected to play a role in malignant transformation. The mechanism by which IRS-1 supports tumor growth is not fully understood, and the argument that IRS-1 merely amplifies the signal from the IGF-1R and/or IR requires further investigation. Almost a decade ago, we reported the presence of nuclear IRS-1 in medulloblastoma clinical samples, which express viral oncoprotein, large T-antigen of human polyomavirus JC (JCV T-antigen). This first demonstration of nuclear IRS-1 was confirmed in several other laboratories. The nuclear IRS-1 was also detected by cells expressing the SV40 T-antigen, v-Src, in immortalized fibroblasts stimulated with IGF-I, in hepatocytes, 32D cells, and in an osteosarcoma cell line. More recently, nuclear IRS-1 was detected in breast cancer cells in association with estrogen receptor alpha (ERα), and in JC virus negative medulloblastoma cells expressing ERβ, further implicating nuclear IRS-1 in cellular transformation. Here, we discuss how nuclear IRS-1 acting on DNA repair fidelity, transcriptional activity, and cell growth can support tumor development and progression.
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影响因子：
12.4
作者：
Gualco E;Urbanska K;Perez-Liz G;Sweet T;Peruzzi F;Reiss K;Del Valle L
通讯作者：
Del Valle L
影响因子：
64.5
作者：
Böhni, R;Riesgo-Escovar, J;Hafen, E
通讯作者：
Hafen, E
影响因子：
4.8
作者：
Belcher, Scott M.;Ma, Xiaolan;Le, Hoa H.
通讯作者：
Le, Hoa H.
影响因子：
64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
4.7
作者：
Kappler, R;Pietsch, T;Scherthan, H
通讯作者：
Scherthan, H