A family-wide assessment of latent STAT transcription factor interactions reveals divergent dimer repertoires.

A family-wide assessment of latent STAT transcription factor interactions reveals divergent dimer repertoires.
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DOI:
10.1016/j.jbc.2023.104703
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发表时间:
2023-05
影响因子:
4.8
通讯作者:
Vinkemeier, Uwe
Vinkemeier, Uwe
中科院分区:
生物学2区
文献类型:
--
作者:
Begitt, Andreas;Krause, Sebastian;Cavey, James R.;Vinkemeier, Doratha E.;Vinkemeier, Uwe

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信号转导和转录激活因子(STAT)蛋白从潜伏的转录因子到激活的转录因子的转化是细胞因子信号转导的核心。在它们信号诱导的酪氨酸磷酸化的触发下,它是一系列细胞因子特异性的STAT同源和异源二聚体的组装,标志着迄今潜伏的蛋白质向转录激活剂转变的关键一步。相比之下,潜在统计信息的结构性自组装以及它如何与激活统计信息的功能相关,人们了解得较少。为了提供更完整的图像,我们开发了一种基于共定位的分析方法,并在活细胞中测试了七种非磷酸化STAT(U-STAT)蛋白的所有28种可能组合。我们鉴定了五个U-STAT同源二聚体--STAT1、STAT3、STAT4、STAT5A和STAT5B-以及两个异源二聚体--STAT1:STAT2和STAT5A:STAT5B--并对支持它们的结合界面的作用力和特征进行了半定量评估。一种STAT蛋白--STAT6--被发现是单体。这种对潜在STAT自组装的全面分析揭示了在激活前后连接STAT二聚的方式的相当大的结构和功能的多样性。
The conversion of signal transducer and activator of transcription (STAT) proteins from latent to active transcription factors is central to cytokine signaling. Triggered by their signal-induced tyrosine phosphorylation, it is the assembly of a range of cytokine-specific STAT homo- and heterodimers that marks a key step in the transition of hitherto latent proteins to transcription activators. In contrast, the constitutive self-assembly of latent STATs and how it relates to the functioning of activated STATs is understood less well. To provide a more complete picture, we developed a co-localization-based assay and tested all 28 possible combinations of the seven unphosphorylated STAT (U-STAT) proteins in living cells. We identified five U-STAT homodimers—STAT1, STAT3, STAT4, STAT5A, and STAT5B—and two heterodimers—STAT1:STAT2 and STAT5A:STAT5B—and performed semi-quantitative assessments of the forces and characterizations of binding interfaces that support them. One STAT protein—STAT6—was found to be monomeric. This comprehensive analysis of latent STAT self-assembly lays bare considerable structural and functional diversity in the ways that link STAT dimerization before and after activation.
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STAT2是一种普遍的细胞因子调节剂,由于其在多个信号传导途径中抑制了STAT1。
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