Schmidt D, Müller S
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, 82152, Martinsried, Germany.
Cell Mol Life Sci. 2003 Dec;60(12):2561-74. doi: 10.1007/s00018-003-3129-1.
Protein inhibitor of activated STATs (PIAS) proteins were initially identified as negative regulators of cytokine signalling that inhibit the activity of STAT-transcription factors. Evidence is accumulating that PIAS proteins function as transcriptional coregulators in various other important cellular pathways, including Wnt signalling, the p53 pathway and steroid hormone signalling. Most interestingly, recent work from several laboratories revealed that PIAS proteins act as E3-like ligases that stimulate the attachment of the ubiquitin-like SUMO modifier to target proteins acting in these pathways. Since in most cases the SUMO ligase activity and the transcriptional coregulator activity are functionally correlated, the PIAS/SUMO pathway appears to be an important mechanism of transcriptional regulation. In this review we will discuss some key findings that exemplify the role of PIAS proteins in the regulation of transcriptional processes and propose a model how the PIAS/ SUMO system may modulate transcriptional activities by mediating the assembly of coactivator or corepressor complexes within distinct subnuclear structures.
活化STAT蛋白的蛋白抑制剂（PIAS）最初被鉴定为细胞因子信号传导的负调节因子，可抑制STAT转录因子的活性。越来越多的证据表明，PIAS蛋白在包括Wnt信号传导、p53途径和类固醇激素信号传导在内的各种其他重要细胞途径中作为转录共调节因子发挥作用。最有趣的是，几个实验室最近的研究表明，PIAS蛋白作为类E3连接酶，刺激泛素样SUMO修饰剂附着于在这些途径中起作用的靶蛋白。由于在大多数情况下，SUMO连接酶活性和转录共调节因子活性在功能上相关，PIAS/SUMO途径似乎是转录调控的重要机制。在这篇综述中，我们将讨论一些关键发现，这些发现例证了PIAS蛋白在转录过程调控中的作用，并提出一个模型，说明PIAS/SUMO系统如何通过介导不同亚核结构内共激活因子或共抑制因子复合物的组装来调节转录活性。
