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首页> 外文期刊>Genes to cells : >Ligand-dependent nucleo-cytoplasmic shuttling of peroxisome proliferator-activated receptors, PPAR alpha and PPAR gamma
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Ligand-dependent nucleo-cytoplasmic shuttling of peroxisome proliferator-activated receptors, PPAR alpha and PPAR gamma

机译：过氧化物酶体增殖物激活受体，PPARα和PPARγ的配体依赖性核质穿梭

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摘要

Peroxisome proliferatoractivated receptors (PPARs) play important roles in diverse biological processes including metabolisms of sugars and lipids and differentiation of cells such as adipocytes. PPARs are transcription factors belonging to the ligand-dependent hormone receptor group. To function as transcription factors, PPARs translocate into nucleus where they associate with transcription apparatus. However, mechanisms underlying nuclear transport of PPARs remain enigmatic. We show here that PPARa and PPAR? dynamically shuttle between nucleus and cytoplasm, although they constitutively and predominantly appear in nucleus. With a series of truncation mutants, we identify that PPAR nuclear transport is mediated by at least two nuclear localization signals (NLSs) in DNA-binding domain (DBD)hinge and activation function 1 (AF1) regions and their respective receptors including importina/beta, importin 7, and an unidentified receptor. PPARs also harbor two nuclear export signals in DBD and ligand-binding domain regions that are recognized by distinct export receptors, calreticulin and CRM1. Moreover, we show that nuclearcytoplasmic shuttling of PPARs is regulated by respective PPAR ligands and Ca2+ concentration. Taken together, we suggest that the multiple pathways for the nuclearcytoplasmic transport of PPARs regulate the biological functions of PPARs in response to external signals.
机译：过氧化物酶体增殖物激活受体（PPAR）在多种生物过程中发挥重要作用，包括糖和脂质的代谢以及细胞（例如脂肪细胞）的分化。 PPAR是属于配体依赖性激素受体组的转录因子。为了起转录因子的作用，PPARs易位入细胞核，并与转录装置结合。但是，PPARs核运输的基础机制仍然是个谜。我们在这里显示PPARa和PPAR？尽管它们主要组成性地出现在细胞核中，但它们在细胞核和细胞质之间动态穿梭。使用一系列的截断突变体，我们确定PPAR核转运是由DNA结合域（DBD）铰链和激活功能1（AF1）区域中的至少两个核定位信号（NLSs）介导的，以及它们各自的受体包括importina / beta ，importin 7和一个未知的受体。 PPAR还在DBD和配体结合结构域区域中包含两个核输出信号，这两个信号被不同的输出受体钙网蛋白和CRM1识别。此外，我们表明，PPAR的核质穿梭由各自的PPAR配体和Ca2 +浓度调节。两者合计，我们建议PPARs的核质质运输的多种途径调节PPARs响应外部信号的生物学功能。

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