Biophysical insights into glucose-dependent transcriptional regulation by PDX1.
Biophysical insights into glucose-dependent transcriptional regulation by PDX1.
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DOI：
10.1016/j.jbc.2022.102623
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发表时间：
2022-12
影响因子：
4.8
通讯作者：
Showalter, Scott A.
中科院分区：
文献类型：
--
作者：
Usher, Emery T.;Showalter, Scott A.
胰腺和十二指肠同源框1（PDX1）是胰腺β细胞中胰岛素葡萄糖依赖性转录的中心调节因子。PDX1转录因子活性是胰腺发育和持续健康不可或缺的;因此，破译导致PDX1激活或失活的细胞信号的复杂网络是理解胰腺疾病病因和开发新疗法的重要一步。尽管对PDX1控制胰岛素表达进行了近30年的研究，但决定PDX1响应葡萄糖功能的分子机制仍然难以捉摸。PDX1的转录激活功能部分受其两个内在无序区域的调节，这对其结构和生物物理特性构成障碍。事实上，许多关于PDX1相互作用、临床突变和翻译后修饰的研究缺乏分子水平的细节。新兴的内在无序区域的定量研究方法和反式激活的精细模型现在使我们能够验证和询问PDX 1的生物化学和生物物理特征，决定其功能。本综述的目的是总结现有的PDX1研究，并进一步产生一个全面的资源，为未来的研究转录控制通过PDX1。
The pancreatic and duodenal homeobox 1 (PDX1) is a central regulator of glucose-dependent transcription of insulin in pancreatic β cells. PDX1 transcription factor activity is integral to the development and sustained health of the pancreas; accordingly, deciphering the complex network of cellular cues that lead to PDX1 activation or inactivation is an important step toward understanding the etiopathologies of pancreatic diseases and the development of novel therapeutics. Despite nearly 3 decades of research into PDX1 control of Insulin expression, the molecular mechanisms that dictate the function of PDX1 in response to glucose are still elusive. The transcriptional activation functions of PDX1 are regulated, in part, by its two intrinsically disordered regions, which pose a barrier to its structural and biophysical characterization. Indeed, many studies of PDX1 interactions, clinical mutations, and posttranslational modifications lack molecular level detail. Emerging methods for the quantitative study of intrinsically disordered regions and refined models for transactivation now enable us to validate and interrogate the biochemical and biophysical features of PDX1 that dictate its function. The goal of this review is to summarize existing PDX1 studies and, further, to generate a comprehensive resource for future studies of transcriptional control via PDX1.
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影响因子：
3.5
作者：
Caetano, L. A.;Santana, L. S.;Teles, M. G.
通讯作者：
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DOI：
10.1073/pnas.1921473117
发表时间：
2020-09-22
影响因子：
11.1
作者：
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DOI：
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发表时间：
2022-01
期刊：
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影响因子：
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作者：
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影响因子：
4.6
作者：
Al-Kandari H;Al-Abdulrazzaq D;Davidsson L;Nizam R;Jacob S;Melhem M;John SE;Al-Mulla F
通讯作者：
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