Intracellular interleukin-1α functionally interacts with histone acetyltransferase complexes
Intracellular interleukin-1α functionally interacts with histone acetyltransferase complexes
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DOI：
10.1074/jbc.m306342200
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发表时间：
2004-02-06
影响因子：
4.8
通讯作者：
Burysek, L
中科院分区：
文献类型：
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作者：
Buryskova, M;Pospisek, M;Burysek, L
白细胞介素-1 α（IL-1 α）是一种通过膜受体在细胞外发挥作用的炎性细胞因子。有趣的是，合成的IL-1 α的很大一部分不是分泌的;相反，它被主动转运到细胞核中。IL-1 α确实被证明参与某些细胞内过程，如增殖、凋亡或迁移的控制，然而，这些作用的机制尚不清楚。在这里，我们表明，细胞内IL-1 α融合的Ga 14 p DNA结合结构域（Gal 4 BD）具有很强的反式激活潜力，可以通过过度表达的转录辅激活因子p300。我们证明了IL-1 α前体通过其N-末端肽（IL-1 NTP）与组蛋白乙酰转移酶p300，PCAF，Gcn 5和接头组件Ada 3相互作用，并且它以非破坏性的方式整合到PCAF-p300复合物中。类似于已知的酸性共活化剂，表达Gal 4 BD/IL-1 NTP的酵母菌株显示出毒性表型，其可以通过消耗佐贺复合物的各种组分来减轻。我们的数据为IL-1 α前体的核靶点提供了第一个确凿的证据，并表明其在转录控制中的新功能。
Interleukin-1alpha (IL-1alpha) is an inflammatory cytokine acting extracellularly via membrane receptors. Interestingly, a significant portion of synthesized IL-1alpha is not secreted; instead, it is actively translocated into the cell nucleus. IL-1alpha was indeed shown to be involved in certain intracellular processes, such as control of proliferation, apoptosis, or migration, however, the mechanisms of such actions are not known. Here we show that intracellular IL-1alpha fused to the Ga14p DNA-binding domain (Gal4BD) possesses strong transactivation potential that can be boosted by overexpression of the transcriptional coactivator p300. We demonstrate that the IL-1alpha precursor interacts via its N-terminal peptide (IL-1NTP) with histone acetyltransferases p300, PCAF, Gcn5 and with the adaptor component Ada3, and that it integrates into the PCAF-p300 complex in a non-destructive manner. In analogy with known acidic coactivators, yeast strains expressing Gal4BD/IL-1NTP display a toxic phenotype that can be relieved by depletion of various components of the SAGA complex. Our data provide the first solid evidence for the nuclear target of the IL-1alpha precursor and suggest its novel function in transcriptional control.