Kandemir Basak, Kurnaz Isil Aksan
Department of Molecular Biology and Genetics, Baskent University, 06790, Etimesgut, Ankara, Turkey.
Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, 27709, USA.
Mol Neurobiol. 2025 Mar;62(3):3293-3304. doi: 10.1007/s12035-024-04432-w. Epub 2024 Sep 13.
ETS domain transcription factor superfamily is highly conserved throughout metazoa and is involved in many aspects of development and tissue morphogenesis, and as such, the deregulation of ETS proteins is quite common in many diseases, including cancer. The PEA3 subfamily in particular has been extensively studied with respect to tumorigenesis and metastasis; however, they are also involved in the development of many tissues with branching morphogenesis, such as lung or kidney development. In this review, we aim to summarize findings from various studies on the role of Pea3 subfamily members in nervous system development in the embryo, as well as their functions in the adult neurons. We further discuss the different signals that were shown to regulate the function of the Pea3 family and indicate how this signal-dependent regulation of Pea3 proteins can generate neuronal circuit specificity through unique gene regulation. Finally, we discuss how these developmental roles of Pea3 proteins relate to their role in tumorigenesis.
ETS结构域转录因子超家族在整个后生动物中高度保守，参与发育和组织形态发生的许多方面，因此，ETS蛋白的失调在包括癌症在内的许多疾病中相当常见。特别是PEA3亚家族，已在肿瘤发生和转移方面得到广泛研究；然而，它们也参与许多具有分支形态发生的组织的发育，如肺或肾的发育。在这篇综述中，我们旨在总结关于Pea3亚家族成员在胚胎神经系统发育中的作用以及它们在成体神经元中的功能的各种研究结果。我们进一步讨论了已被证明调节Pea3家族功能的不同信号，并指出这种依赖信号的Pea3蛋白调节如何通过独特的基因调控产生神经元回路特异性。最后，我们讨论了Pea3蛋白的这些发育作用与其在肿瘤发生中的作用之间的关系。
