A novel mutation in β integrin reveals an integrin-mediated interaction between the extracellular matrix and cki-1/p27KIP1.
A novel mutation in β integrin reveals an integrin-mediated interaction between the extracellular matrix and cki-1/p27KIP1.
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DOI：
10.1371/journal.pone.0042425
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lee M
中科院分区：
文献类型：
--
作者：
Kihira S;Yu EJ;Cunningham J;Cram EJ;Lee M
细胞与细胞外基质（ECM）的相互作用在维持组织形状和调节细胞粘附、分化和增殖等细胞行为方面起着重要作用。ECM影响体内细胞周期的机制知之甚少。在此，我们证明β整合素PAT-3调节CKI-1的定位和表达，CKI-1是一种C.细胞周期蛋白依赖性激酶抑制剂p27 KIP 1的elegans同源物。在表达野生型PAT-3的线虫中，CKI-1：：GFP主要定位于皮下细胞中的核仁，而在表达具有缺陷性剪接连接的突变体pat-3的动物中，CKI-1：：GFP在核质中出现聚集和紊乱。RNAi分析将细胞粘附基因与CKI-1的调节联系起来。unc-52/串珠素、ina-1/α整合素、pat-4/ILK和unc-97/PINCH的RNAi导致CKI-1：：GFP定位异常。另外的RNAi实验显示，SCF E3泛素-连接酶复合物基因skpt-1/SKP 2、cul-1/CUL 1和lin-23/F-box是CKI-1正确定位和表达所必需的，这表明整合素信号传导和SCF E3连接酶共同作用以调节CKI-1的细胞分布。这些数据还表明，整合素在维持细胞中适当的CKI-1/p27 KIP 1水平中起主要作用。整合素信号通路的紊乱可能导致SCF连接酶活性的抑制、CKI-1/p27 KIP 1的错误定位和升高。这些结果表明，粘附信号是至关重要的细胞周期调控在体内。
The cell-extracellular matrix (ECM) interaction plays an essential role in maintaining tissue shapes and regulates cell behaviors such as cell adhesion, differentiation and proliferation. The mechanism by which the ECM influences the cell cycle in vivo is poorly understood. Here we demonstrate that the β integrin PAT-3 regulates the localization and expression of CKI-1, a C. elegans homologue of the cyclin dependent kinase inhibitor p27KIP1. In nematodes expressing wild type PAT-3, CKI-1::GFP localizes primarily to nucleoli in hypodermal cells, whereas in animals expressing mutant pat-3 with a defective splice junction, CKI-1::GFP appears clumped and disorganized in nucleoplasm. RNAi analysis links cell adhesion genes to the regulation of CKI-1. RNAi of unc-52/perlecan, ina-1/α integrin, pat-4/ILK, and unc-97/PINCH resulted in abnormal CKI-1::GFP localization. Additional RNAi experiments revealed that the SCF E3 ubiquitin-ligase complex genes, skpt-1/SKP2, cul-1/CUL1 and lin-23/F-box, are required for the proper localization and expression of CKI-1, suggesting that integrin signaling and SCF E3 ligase work together to regulate the cellular distribution of CKI-1. These data also suggest that integrin plays a major role in maintaining proper CKI-1/p27KIP1 levels in the cell. Perturbed integrin signaling may lead to the inhibition of SCF ligase activity, mislocalization and elevation of CKI-1/p27KIP1. These results suggest that adhesion signaling is crucial for cell cycle regulation in vivo.
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DOI：
10.1083/jcb.139.6.1583
发表时间：
1997-12-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Belkin AM;Retta SF;Pletjushkina OY;Balzac F;Silengo L;Fassler R;Koteliansky VE;Burridge K;Tarone G
通讯作者：
Tarone G
DOI：
10.1083/jcb.121.1.171
发表时间：
1993-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Balzac F;Belkin AM;Koteliansky VE;Balabanov YV;Altruda F;Silengo L;Tarone G
通讯作者：
Tarone G
影响因子：
21.3
作者：
Carrano, AC;Eytan, E;Pagano, M
通讯作者：
Pagano, M
肝脏容量测定即插即用：使用 ImageJ 自行操作。
影响因子：
2.6
作者：
Dello, Simon A. W. G.;van Dam, Ronald M.;Slangen, Jules J. G.;de Poll, Marcel C. G. van;Bemelmans, Marc H. A.;Greve, Jan Willem W. M.;Beets-Tan, Regina G. H.;Wigmore, Stephen J.;Dejong, Cornelis H. C.
通讯作者：
Dejong, Cornelis H. C.
DOI：
10.1083/jcb.153.7.1381
发表时间：
2001-06-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carrano AC;Pagano M
通讯作者：
Pagano M