过氧物酶体proliferator-activated受体、辅活化因子和下游目标。
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朱七C, Y, Reddy JK
过氧物酶体proliferator-activated受体、辅活化因子和下游目标。
细胞生物化学Biophys。2000; 32春天:187 - 204。
- PubMed ID
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11330046 (在PubMed]
- 文摘
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肝实质细胞过氧化物酶体增殖反应结构多样化摘要化合物指定为过氧物酶体扩散(PP)。持续的过氧物酶体增殖诱导和过氧化物酶病脂肪酸在老鼠和老鼠机会系统导致肝肿瘤的发展。两个机械的问题是重要的考虑:说明上游事件负责组织和物种的特定的感应PPs的多向性的响应特征;和下游事件的描述与过氧物酶体增殖有关,在肝肿瘤的发展及其作用敏感的物种,过氧物酶体增殖的感应。过氧物酶体增殖的感应是由PP-activatedα受体(PPARα),一群成员转录因子调节与脂类代谢相关基因的表达和脂肪细胞的分化。三个同形像的核受体家族,即PPARα,PPARγ,和PPARδ(也称为β),已经被确认为单独的基因的产物。尽管PPARα负责PP-induced多向性的反应,PPARγ似乎参与脂肪形成和分化,但与PPARγ相关联的事件并不直接涉及过氧化物酶体和过氧物酶体增殖。PPARs二聚化和9-cis视黄酸受体(RXR)和绑定页响应元素(s) (ppr)在目标基因启动子启动诱导转录活动。组织和物种对PPs的反应取决于药物动力学,相对丰富的PPAR同形像,自然PPRE目标基因的上游地区,竞争的程度或相声中核转录因子PPAR heterodimerization伴侣类维生素a X受体辅活化因子的调节作用和辅阻遏物PPARs ligand-dependent转录。使用PPAR作为诱饵在酵母2台混合动力系统中,作者最近克隆老鼠类固醇受体coactivator-1 (SRC-1)和PPAR-binding蛋白质(PBP),并确认他们是PPAR辅活化因子。 Both SRC-1 and PBP contain LXXLL signature motifs, considered necessary and sufficient for the binding of coactivators to nuclear receptors. A multifaceted approach, which includes the identification of additional coactivators that may be responsible for cell specific transcriptional activation of PPAR-mediated target genes, and generation of genetically modified animals (transgenic and gene disrupted), will be necessary to gain more insight into the upstream and downstream targets responsible for the induction of early and delayed PP-induced pleiotropic responses. In this context, it is important to note that mice deficient in fatty acyl-CoA oxidase, the first and rate-limiting enzyme of the peroxisomal beta-oxidation system, revealed that this enzyme is indispensable for the physiological regulation of PPAR alpha, and the absence of this enzyme leads to sustained transcriptional activation of genes regulated by this receptor.
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