Ube2l3 gene expression is modulated by activation of the aryl hydrocarbon receptor: implications for p53 ubiquitination.
Ube2l3 gene expression is modulated by activation of the aryl hydrocarbon receptor: implications for p53 ubiquitination.
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DOI：
10.1016/j.bcp.2010.05.007
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发表时间：
2010-09-15
影响因子：
5.8
通讯作者：
Elizondo G
中科院分区：
文献类型：
--
作者：
Reyes-Hernández OD;Mejía-García A;Sánchez-Ocampo EM;Cabañas-Cortés MA;Ramírez P;Chávez-González L;Gonzalez FJ;Elizondo G
暴露于2，3，7，8-四氯二苯并对二恶英（TCDD），一种卤代芳烃和环境污染物，导致几种有害影响，包括胎儿畸形和癌症。这些作用是由芳香烃受体（AhR）介导的，这是一种配体激活的受体，可调节编码外源性代谢酶的基因的表达。一些报告表明AhR的功能超出了适应性化学反应。在本研究中，我们分析和比较了C57 BL/6 N野生型（WT）和Ahr基因敲除小鼠的基因表达谱。DNA微阵列和定量RT-PCR分析揭示了参与泛素-蛋白酶体系统（UPS）的基因表达的变化。UPS在细胞内稳态控制中具有重要作用，并且该途径的功能障碍已经涉及几种人类病理学的发展。蛋白质泛素化是一个多步骤的酶促过程，其调节修饰蛋白质的稳定性、功能和/或定位。该系统通过共价修饰高度调节。然而，关于编码泛素（Ub）蛋白的基因的转录调控的信息很少。因此，我们研究了AhR在调节UPS和调节Ube 2l 3转录（一种E2泛素结合酶）中的作用，以及对p53降解的影响。我们的研究结果表明，AhR失活降低肝脏蛋白酶体活性，可能是由于下调几个蛋白酶体亚基的表达。另一方面，AhR激活通过控制Ube 2l 3基因表达增加Ube 2l 3 mRNA和蛋白水平，导致p53泛素化和降解增加。与此一致，细胞凋亡的诱导被AhR激活减弱。
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a halogenated aromatic hydrocarbon and environmental contaminant, results in several deleterious effects, including fetal malformation and cancer. These effects are mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated receptor that regulates the expression of genes encoding xenobiotic-metabolizing enzymes. Several reports suggest that AhR function is beyond the adaptive chemical response. In the present study, we analyzed and compared gene expression profiles of C57BL/6N wild-type (WT) and Ahr-null mice. DNA microarray and quantitative RT-PCR analyses revealed changes in the expression of genes involved in the ubiquitin-proteasome system (UPS). UPS has an important role in cellular homeostasis control and dysfunction of this pathway has been implicated in the development of several human pathologies. Protein ubiquitination is a multi-step enzymatic process that regulates the stability, function, and/or localization of the modified proteins. This system is highly regulated post-translationally by covalent modifications. However, little information regarding the transcriptional regulation of the genes encoding ubiquitin (Ub) proteins is available. Therefore, we investigated the role of the AhR in modulation of the UPS and regulation of Ube2l3 transcription, an E2 ubiquitin-conjugating enzyme, as well as the effects on p53 degradation. Our results indicate that AhR inactivation decreases on liver proteasome activity, probably due to a down-regulation on the expression of several proteasome subunits. On the other hand, AhR activation increases Ube2l3 mRNA and protein levels by controlling Ube2l3 gene expression, resulting in increased p53 ubiquitination and degradation. In agreement with this, induction of apoptosis was attenuated by the AhR activation.
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影响因子：
64.5
作者：
SCHEFFNER, M;HUIBREGTSE, JM;HOWLEY, PM
通讯作者：
HOWLEY, PM
影响因子：
9.2
作者：
Freemont, PS
通讯作者：
Freemont, PS
影响因子：
4
作者：
Garside, Helen;Waters, Charlotte;Ray, David
通讯作者：
Ray, David
影响因子：
4.4
作者：
Lee, SH;Lee, DY;Kim, CW
通讯作者：
Kim, CW
影响因子：
3.5
作者：
Rodríguez-Sosa, M;Elizondo, G;Vega, L
通讯作者：
Vega, L