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首页> 外文期刊>Cellular Signalling >Cellular retinoic acid binding protein I mediates rapid non-canonical activation of ERK1/2 by all-trans retinoic acid
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Cellular retinoic acid binding protein I mediates rapid non-canonical activation of ERK1/2 by all-trans retinoic acid

机译:细胞视黄酸结合蛋白I通过全反式视黄酸介导ERK1 / 2的快速非规范激活

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摘要

All-trans retinoic acid (atRA), one of the active ingredients of vitamin A, exerts canonical activities to regulate gene expression mediated by nuclear RA receptors (RARs). AtRA could also elicit certain non-canonical activities including, mostly, rapid activation of extracellular signal regulated kinase 1/2 (ERK1/2); but the mechanism was unclear. In this study, we have found that cellular retinoic acid binding protein I (CRABPI) mediates the non-canonical, RAR- and membrane signal-independent activation of ERK1/2 by atRA in various cellular backgrounds. In the context of embryonic stem cells (ESCs), atRA/CRABPI-dependent ERK1/2 activation rapidly affects ESC cell cycle, specifically to expand the G1 phase. This is mediated by ERK stimulation resulting in dephosphorylation of nuclear p27, which elevates nuclear p27 protein levels to block G1 progression to S phase. This is the first study to identify CRABPI as the mediator for non-canonical activation of ERK1/2 by atRA, and demonstrate a new functional role for CRABPI in modulating ESC cell cycle progression.
机译:全反式维甲酸(atRA)是维生素A的活性成分之一,发挥规范的作用来调节由核RA受体(RAR)介导的基因表达。 AtRA还可以引起某些非规范性活动,主要包括细胞外信号调节激酶1/2(ERK1 / 2)的快速激活。但机制尚不清楚。在这项研究中,我们发现细胞视黄酸结合蛋白I(CRABPI)介导了atRA在各种细胞背景下对ERK1 / 2的非经典,非RAR和膜信号依赖性激活。在胚胎干细胞(ESC)的背景下,依赖于ATRA / CRABPI的ERK1 / 2激活会迅速影响ESC细胞周期,特别是扩大G1期。这是由ERK刺激介导的,导致核p27的去磷酸化,从而提高了核p27蛋白的水平,从而阻止了G1进入S期。这是第一项鉴定CRABPI为atRA非正常激活ERK1 / 2的介质的研究,并证明CRABPI在调节ESC细胞周期进程中的新功能。

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