A transcriptional cross-talk between RhoA and c-Myc inhibits the RhoA/Rock-dependent cytoskeleton.
A transcriptional cross-talk between RhoA and c-Myc inhibits the RhoA/Rock-dependent cytoskeleton.
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DOI：
10.1038/onc.2010.134
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发表时间：
2010-07-01
期刊：
影响因子：
8
通讯作者：
Bustelo, X. R.
中科院分区：
文献类型：
--
作者：
Sauzeau, V.;Berenjeno, I. M.;Citterio, C.;Bustelo, X. R.
GTdR RhoA参与许多细胞过程，包括细胞骨架组织、有丝分裂和肿瘤发生。我们之前已经证明，RhoA的致癌版本（Q63 L突变体）的转化活性高度依赖于转录因子c-Myc。与RhoA途径中的这些积极作用相反，我们在这里表明，c-Myc对RhoAQ 63 L及其下游效应子丝氨酸/苏氨酸激酶Rock诱导的F-肌动蛋白细胞骨架产生负面影响。这种效应需要激活一个转录程序，需要与RhoA衍生的信号的协同相互作用，包括上调GTdR Cdc 42及其下游元件Pak 1以及抑制特定的整合素亚基。c-Myc在F-肌动蛋白细胞骨架中的负面作用通过建立细胞与细胞的接触而消除，这种作用分别与转录后和转录水平上的Pak 1和整合素水平的拯救相关。这些结果揭示了RhoA和c-Myc癌基因之间存在一个迄今未知的信号反馈回路，该回路有助于维持癌细胞中的流体细胞骨架动力学。
The GTPase RhoA participates in a number of cellular processes, including cytoskeletal organization, mitogenesis and tumorigenesis. We have previously shown that the transforming activity of an oncogenic version of RhoA (Q63L mutant) was highly dependent on the transcriptional factor c–Myc. In contrast to these positive effects in the RhoA route, we show here that c–Myc affects negatively the F–actin cytoskeleton induced by RhoAQ63L and its downstream effector, the serine/threonine kinase Rock. This effect entails the activation of a transcriptional program that requires synergistic interactions with RhoA–derived signals and that includes the upregulation of the GTPase Cdc42 and its downstream element Pak1 as well as the repression of specific integrin subunits. The negative effects of c–Myc in the F–actin cytoskeleton are eliminated by the establishment of cell–to–cell contacts, an effect associated with the rescue of Pak1 and integrin levels at the post–transcriptional and transcriptional levels, respectively. These results reveal the presence of a hitherto unknown signaling feed–back loop between RhoA and c–Myc oncogenes that can contribute to maintain fluid cytoskeletal dynamics in cancer cells.
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DOI：
10.1083/jcb.200605135
发表时间：
2007-01-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Sahai E;Garcia-Medina R;Pouysségur J;Vial E
通讯作者：
Vial E
影响因子：
3.3
作者：
Hatzoglou, Anastassia;Ader, Isabelle;de Gunzburg, Jean
通讯作者：
de Gunzburg, Jean
影响因子：
5.3
作者：
Riento, K;Guasch, RM;Ridley, AJ
通讯作者：
Ridley, AJ
影响因子：
11.4
作者：
Shiio, Y;Donohoe, S;Eisenman, RN
通讯作者：
Eisenman, RN
影响因子：
4.8
作者：
Amano, M;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K