TCF11 Has a Potent Tumor-Repressing Effect Than Its Prototypic Nrf1α by Definition of Both Similar Yet Different Regulatory Profiles, With a Striking Disparity From Nrf2.
TCF11 Has a Potent Tumor-Repressing Effect Than Its Prototypic Nrf1α by Definition of Both Similar Yet Different Regulatory Profiles, With a Striking Disparity From Nrf2.
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根据相似但不同的监管概况的定义，TCF11 比其原型 Nrf1α 具有更强大的肿瘤抑制作用，与 Nrf2 存在显着差异
DOI：
10.3389/fonc.2021.707032
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Wang M;Ren Y;Hu S;Liu K;Qiu L;Zhang Y
Nrf 1和Nrf 2作为两种主要的CNC-bZIP转录因子，调节涉及多种生物学功能的相似但不同的靶点，以维持细胞内稳态和器官完整性。值得注意的是，Nrf 1独特的局部生物学行为使其功能比Nrf 2更复杂，因为它允许交替转录和选择性剪接以产生多种同种型（例如，TCF 11，Nrf1α）。为了更好地理解它们在不同调控谱中的相似性和差异，本文通过Flp-In™ T-REx™-293系统建立了用于稳定表达TCF 11、TCF 11 ΔN、Nrf 1 α或Nrf 2的所有四种不同细胞模型，然后通过转录组测序鉴定。进一步的分析显示，Nrf 1 α和TCF 11具有相似但不同的调控特征，尽管两者基本上都有助于对其共同靶点的正调控，这与Nrf 2的调控不同。Nrf 1和Nrf 2在这些基因调控中的这种差异通过仔细检查其特异性和/或共同靶基因的全面功能注释进一步证实。相反，TCF 11 ΔN突变体，由TCF 11 N端氨基酸2-156缺失产生，类似于Nrf 2，具有基本一致的结构和功能。有趣的是，我们进一步的实验证据表明，相对于Nrf 1 α，TCF 11是一种有效的肿瘤抑制因子，尽管两种亚型都具有预防肿瘤恶性生长的一致能力，并上调那些对提高肝细胞癌患者生存率至关重要的基因。
Nrf1 and Nrf2, as two principal CNC-bZIP transcription factors, regulate similar but different targets involved in a variety of biological functions for maintaining cell homeostasis and organ integrity. Of note, the unique topobiological behavior of Nrf1 makes its functions more complicated than Nrf2, because it is allowed for alternatively transcribing and selectively splicing to yield multiple isoforms (e.g., TCF11, Nrf1α). In order to gain a better understanding of their similarities and differences in distinct regulatory profiles, all four distinct cell models for stably expressing TCF11, TCF11ΔN, Nrf1α or Nrf2 have been herein established by an Flp-In™ T-REx™-293 system and then identified by transcriptomic sequencing. Further analysis revealed that Nrf1α and TCF11 have similar yet different regulatory profiles, although both contribute basically to positive regulation of their co-targets, which are disparate from those regulated by Nrf2. Such disparity in those gene regulations by Nrf1 and Nrf2 was further corroborated by scrutinizing comprehensive functional annotation of their specific and/or common target genes. Conversely, the mutant TCF11ΔN, resulting from a deletion of the N-terminal amino acids 2–156 from TCF11, resembles Nrf2 with the largely consistent structure and function. Interestingly, our further experimental evidence demonstrates that TCF11 acts as a potent tumor-repressor relative to Nrf1α, albeit both isoforms possess a congruous capability to prevent malignant growth of tumor and upregulate those genes critical for improving the survival of patients with hepatocellular carcinoma.
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定义Cap'n'Collar转录因子NRF1，NRF2和NRF3的功能靶标。
DOI：
10.3390/antiox9101025
发表时间：
2020-10-21
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Ibrahim L;Mesgarzadeh J;Xu I;Powers ET;Wiseman RL;Bollong MJ
通讯作者：
Bollong MJ
影响因子：
3.8
作者：
Anaya, Jordan
通讯作者：
Anaya, Jordan
影响因子：
2.4
作者：
Berginc, Katja;Kristl, Albin
通讯作者：
Kristl, Albin
影响因子：
5.3
作者：
Chen, LY;Kwong, M;Chan, JY
通讯作者：
Chan, JY
核因子 - 果皮2相关因子1调节肝细胞中蛋白酶体基因的表达，并预防小鼠内质网应激和脂肪变性。
DOI：
10.1111/febs.12350
发表时间：
2013-08
期刊：
The FEBS journal
影响因子：
--
作者：
Lee CS;Ho DV;Chan JY
通讯作者：
Chan JY