Maximal aryl hydrocarbon receptor activity depends on an interaction with the retinoblastoma protein
Maximal aryl hydrocarbon receptor activity depends on an interaction with the retinoblastoma protein
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DOI：
10.1124/mol.59.4.664
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发表时间：
2001-04-01
影响因子：
3.6
通讯作者：
Levine, A
中科院分区：
文献类型：
--
作者：
Elferink, CJ;Ge, NL;Levine, A
芳烃受体（AhR）属于基本螺旋-环-螺旋/周期性/AhR核转运子/简单（Per-Arnt-Sim）转录因子家族，其在发育和组织稳态期间调节关键功能。在这个家族中，AhR是唯一一个对配体结合有条件激活的成员，典型的是2，3，7，8-四氯二苯并-对-二恶英（TCDD）。我们最近证明了AhR与视网膜母细胞瘤蛋白（pRb）相互作用。本报告提供的证据表明，AhR蛋白中的LXCXE基序赋予pRb结合，这是必要的最大TCDD诱导大鼠5L肝癌细胞的G（1）阻滞。这些数据支持一种机制，即pRb似乎调节G（1）细胞周期的进程，而不是直接抑制E2 F介导的转录。此外，结果表明，AhR-pRb相互作用调节TCDD诱导的CYP 1A 1，这表明pRb可能是一个通用的AhR辅激活剂。
The aryl hydrocarbon receptor (AhR) belongs to the basic helix-loop-helix/periodicity/AhR nuclear translocator/simple-minded (Per-Arnt-Sim) family of transcription factors that regulate critical functions during development and tissue homeostasis. Within this family, the AhR is the only member conditionally activated in response to ligand binding, typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We recently demonstrated that the AhR interacts with the retinoblastoma protein (pRb). This report presents evidence that a LXCXE motif in the AhR protein confers pRb binding, which is necessary for maximal TCDD induced G(1) arrest in rat 5L hepatoma cells. The data support a mechanism whereby pRb seems to regulate G(1) cell cycle progression distinct from the direct repression of E2F-mediated transcription. Furthermore, the results indicate that the AhR-pRb interaction regulates TCDD induction of CYP1A1, suggesting that pRb may be a general AhR coactivator.