Erk1/2 MAP kinases are required for epidermal G2/M progression.
Erk1/2 MAP kinases are required for epidermal G2/M progression.
复制标题
DOI：
10.1083/jcb.200804038
复制
发表时间：
2009-05-04
期刊：
影响因子：
--
通讯作者：
Khavari PA
中科院分区：
文献类型：
--
作者：
Dumesic PA;Scholl FA;Barragan DI;Khavari PA
Erk 1/2丝裂原活化蛋白激酶（MAPK）在人类癌症中经常被过度活化，它们影响多个过程，包括增殖。然而，Erk 1/2损失在正常上皮组织中的影响，大多数细胞外信号调节激酶（Erk）相关肿瘤的设置，是未知的。在表皮中，Erk 1或Erk 2单独缺失没有影响，而同时Erk 1/2缺失抑制细胞分裂，表明这些MAPK是正常组织自我更新所必需的。由Erk 1/2损失引起的生长抑制通过重新引入Erk 2而不是通过激活促进G1细胞周期进展的Erk效应子来挽救。与成纤维细胞不同，Erk 1/2的缺失降低了细胞周期蛋白D1的表达并诱导G1/S期阻滞，上皮细胞中Erk 1/2的缺失降低了细胞周期蛋白B1和c-Fos的表达并诱导G2/M期阻滞，同时破坏了以细胞周期蛋白B1-Cdc 2为中心的基因调控网络。因此，需要Erk 1/2活性的细胞周期阶段因细胞类型而异，Erk 1/2在上皮细胞中起作用，使其能够通过G2/M进展。
Erk1/2 mitogen-activated protein kinases (MAPKs) are often hyperactivated in human cancers, where they affect multiple processes, including proliferation. However, the effects of Erk1/2 loss in normal epithelial tissue, the setting of most extracellular signal-regulated kinase (Erk)–associated neoplasms, are unknown. In epidermis, loss of Erk1 or Erk2 individually has no effect, whereas simultaneous Erk1/2 depletion inhibits cell division, demonstrating that these MAPKs are necessary for normal tissue self-renewal. Growth inhibition caused by Erk1/2 loss is rescued by reintroducing Erk2, but not by activating Erk effectors that promote G1 cell cycle progression. Unlike fibroblasts, in which Erk1/2 loss decreases cyclin D1 expression and induces G1/S arrest, Erk1/2 loss in epithelial cells reduces cyclin B1 and c-Fos expression and induces G2/M arrest while disrupting a gene regulatory network centered on cyclin B1–Cdc2. Thus, the cell cycle stages at which Erk1/2 activity is required vary by cell type, with Erk1/2 functioning in epithelial cells to enable progression through G2/M.
登录
查看更多内容
影响因子：
82.9
作者：
Choate, KA;Medalie, DA;Khavari, PA
通讯作者：
Khavari, PA
影响因子：
5.6
作者：
Gazel, Alix;Nijhawan, Rajiv I.;Blumenberg, Miroslav
通讯作者：
Blumenberg, Miroslav
影响因子：
5.3
作者：
Hyun, Joogyung;Becam, Isabelle;Bohmann, Dirk
通讯作者：
Bohmann, Dirk
影响因子：
4.3
作者：
Lazarov, Mirella;Green, Cheryl L.;Khavari, Paul A.
通讯作者：
Khavari, Paul A.
影响因子：
4.1
作者：
Frödin, M;Gammeltoft, S
通讯作者：
Gammeltoft, S