ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma-lamin A complexes.
ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma-lamin A complexes.
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DOI：
10.1083/jcb.201004067
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发表时间：
2010-11-29
期刊：
影响因子：
--
通讯作者：
Crespo P
中科院分区：
文献类型：
--
作者：
Rodríguez J;Calvo F;González JM;Casar B;Andrés V;Crespo P
当在细胞核中时，ERK1/2将视网膜母细胞瘤蛋白从纤层蛋白A中移除，促进其快速磷酸化。作为细胞增殖等基本细胞过程的协调者，ERK1/2丝裂原活化蛋白激酶信号影响细胞周期调节。a型层粘连蛋白是核基质的主要成分，它还通过未知的机制控制细胞周期机制。在本文中，我们揭示了ERK1/2和层粘胶蛋白a之间的功能联系，从而调节细胞周期进程。我们证明层粘胶蛋白A作为ERK1/2和视网膜母细胞瘤（Rb）蛋白的互斥dock。我们的研究结果表明，ERK1/2进入细胞核后，立即将Rb从其与层蛋白A的相互作用中移除，从而促进其快速磷酸化，从而促进E2F的激活和细胞周期进入。有趣的是，这些作用与ERK1/2激酶活性无关。我们还表明，细胞转化和肿瘤细胞增殖依赖于层状蛋白A和核ERK1/2水平之间的平衡，这决定了Rb磷酸化/失活的可及性。
When in the nucleus, ERK1/2 dislodges the retinoblastoma protein from lamin A, facilitating its rapid phosphorylation. As orchestrators of essential cellular processes like proliferation, ERK1/2 mitogen-activated protein kinase signals impact on cell cycle regulation. A-type lamins are major constituents of the nuclear matrix that also control the cell cycle machinery by largely unknown mechanisms. In this paper, we disclose a functional liaison between ERK1/2 and lamin A whereby cell cycle progression is regulated. We demonstrate that lamin A serves as a mutually exclusive dock for ERK1/2 and the retinoblastoma (Rb) protein. Our results reveal that, immediately after their postactivation entrance in the nucleus, ERK1/2 dislodge Rb from its interaction with lamin A, thereby facilitating its rapid phosphorylation and consequently promoting E2F activation and cell cycle entry. Interestingly, these effects are independent of ERK1/2 kinase activity. We also show that cellular transformation and tumor cell proliferation are dependent on the balance between lamin A and nuclear ERK1/2 levels, which determines Rb accessibility for phosphorylation/inactivation.
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影响因子：
5.3
作者：
Kerkhoff, E;Rapp, UR
通讯作者：
Rapp, UR
DOI：
10.1073/pnas.0403250101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Johnson, BR;Nitta, RT;Kennedy, BK
通讯作者：
Kennedy, BK
影响因子：
11.4
作者：
Casar, Berta;Sanz-Moreno, Victoria;Crespo, Piero
通讯作者：
Crespo, Piero
影响因子：
3.3
作者：
Markiewicz, E;Dechat, T;Hutchison, CJ
通讯作者：
Hutchison, CJ
影响因子：
4.8
作者：
Ajenjo, N;Aaronson, DS;Crespo, P
通讯作者：
Crespo, P