Krüppel-like Factor-9 and Krüppel-like Factor-13: Highly Related, Multi-Functional, Transcriptional Repressors and Activators of Oncogenesis.
Krüppel-like Factor-9 and Krüppel-like Factor-13: Highly Related, Multi-Functional, Transcriptional Repressors and Activators of Oncogenesis.
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DOI：
10.3390/cancers15235667
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发表时间：
2023-11-30
期刊：
影响因子：
5.2
通讯作者：
Simmen, Rosalia C M
中科院分区：
文献类型：
--
作者：
Simmen, Frank A;Alhallak, Iad;Simmen, Rosalia C M
Krüppel 样因子 9 (KLF9) 和 Krüppel 样因子 13 (KLF13) 是高度相关的蛋白质，在多种组织和多种病理生理状态（包括瘤形成）中充当特定靶基因库的诱导剂和/或抑制因子。在这里，我们描述了 KLF9 和 KLF13 的显着特征，这是有关蛋白质在癌症发展和治疗反应中的作用的当前最先进的研究，以及该领域需要进一步探索的领域。这些旁系同源蛋白值得对多种癌症进行进一步研究，以及它们在抑制或促进增殖和转移表型方面的多重作用，以及可能参与肿瘤微环境中的免疫细胞生物学。特异性蛋白/Krüppel 样因子（SP/KLF 家族）是转录调节因子的保守家族。这些蛋白质在其羧基末端共享三个高度保守、连续的锌指，这是与 DNA 中的顺式元件结合所必需的。每个 SP/KLF 蛋白在其氨基末端和羧基末端区域内都有独特的一级序列，正是这些区域与共激活子、共阻遏物和染色质修饰蛋白相互作用，以支持靶基因的转录激活和抑制。 Krüppel 样因子 9 (KLF9) 和 Krüppel 样因子 13 (KLF13) 是 SP/KLF 家族中最小的两个成员，是旁系同源的，在后生动物进化早期出现，并且高度保守。矛盾的是，虽然 KLF9 和 KLF13 在一级序列上最相似，但在靶细胞中却显示出许多不同的作用。在本文中，我们总结了通过对分化、促炎和抗炎途径、氧化应激和肿瘤免疫细胞浸润的独特作用来确定 KLF9（以及较小程度的 KLF13）在肿瘤抑制或促进中的作用的工作。我们还强调了 miRNA、lncRNA 和环状 RNA 的巨大多样性，它们为普遍存在的肿瘤特异性抑制 KLF9 mRNA 和蛋白提供了机制。 KLF9 和 KLF13 在癌症生物学中的阐明可能为理解肿瘤发生及其预防和治疗提供新的进展。
Krüppel-like Factor-9 (KLF9) and Krüppel-like Factor-13 (KLF13) are highly related proteins that function as inducers and/or repressors of specific target gene repertoires in a variety of tissues and in diverse pathophysiological states, including neoplasia. Here, we describe the salient features of KLF9 and KLF13, the current state-of-the-art research regarding both protein’s actions in cancer development and response to therapies, and where the field requires further exploration. These paralogous proteins warrant further study for multiple cancers, and with respect to their multiplicities of action in suppression or promotion of proliferative and metastatic phenotypes, and likely involvement in immune cell biology within the tumor microenvironment. Specificity Proteins/Krüppel-like Factors (SP/KLF family) are a conserved family of transcriptional regulators. These proteins share three highly conserved, contiguous zinc fingers in their carboxy-terminus, requisite for binding to cis elements in DNA. Each SP/KLF protein has unique primary sequence within its amino-terminal and carboxy-terminal regions, and it is these regions which interact with co-activators, co-repressors, and chromatin-modifying proteins to support the transcriptional activation and repression of target genes. Krüppel-like Factor 9 (KLF9) and Krüppel-like Factor 13 (KLF13) are two of the smallest members of the SP/KLF family, are paralogous, emerged early in metazoan evolution, and are highly conserved. Paradoxically, while most similar in primary sequence, KLF9 and KLF13 display many distinct roles in target cells. In this article, we summarize the work that has identified the roles of KLF9 (and to a lesser degree KLF13) in tumor suppression or promotion via unique effects on differentiation, pro- and anti-inflammatory pathways, oxidative stress, and tumor immune cell infiltration. We also highlight the great diversity of miRNAs, lncRNAs, and circular RNAs which provide mechanisms for the ubiquitous tumor-specific suppression of KLF9 mRNA and protein. Elucidation of KLF9 and KLF13 in cancer biology is likely to provide new inroads to the understanding of oncogenesis and its prevention and treatments.
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影响因子：
5
作者：
Kennedy, Clare L. M.;Price, Emily M.;Mifsud, Karen R.;Salatino, Silvia;Sharma, Eshita;Engledow, Simon;Broxholme, John;Goss, Hannah M.;Reul, Johannes M. H. M.
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作者：
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DOI：
10.1084/jem.20101527
发表时间：
2011-05-09
期刊：
The Journal of experimental medicine
影响因子：
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通讯作者：
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影响因子：
4.6
作者：
Drepanos, Laura;Gans, Ian M.;Grendler, Janelle;Guitar, Sophia;Fuqua, J. Heath;Maki, Nathaniel J.;Tilden, Andrea R.;Graber, Joel H.;Coffman, James A.
通讯作者：
Coffman, James A.
DOI：
10.1002/stem.1875
发表时间：
2015-03
期刊：
Stem cells (Dayton, Ohio)
影响因子：
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作者：
Cvoro A;Devito L;Milton FA;Noli L;Zhang A;Filippi C;Sakai K;Suh JH;H Sieglaff D;Dhawan A;Sakai T;Ilic D;Webb P
通讯作者：
Webb P