Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, 50612, Republic of Korea; Department of Physiology, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea.
Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, 50612, Republic of Korea.
Adv Biol Regul. 2021 Jan;79:100777. doi: 10.1016/j.jbior.2020.100777. Epub 2020 Dec 29.
OCT4 (also known as Oct3 and Oct3/4), which is encoded by Pou5f1, is expressed in early embryonic cells and plays an important role in early development, pluripotency maintenance, and self-renewal of embryonic stem cells. It also regulates the reprogramming of somatic cells into induced pluripotent stem cells. Several OCT4-binding proteins, including SOX2 and NANOG, reportedly regulate gene transcription in stem cells. An increasing number of evidence suggests that not only gene transcription but also post-translational modifications of OCT4 play a pivotal role in regulating the expression and activity of OCT4. For instance, ubiquitination and sumoylation have been reported to regulate OCT4 protein stability. In addition, the phosphorylation of Ser347 in OCT4 also stabilizes the OCT4 protein level. Recently, we identified KAP1 as an OCT4-binding protein and reported the KAP1-mediated regulation of OCT4 protein stability. KAP1 overexpression led to an increased proliferation of mouse embryonic stem cells and promoted the reprogramming of somatic cells resulting in induced pluripotent stem cells. In this review, we discuss how the protein stability and function of OCT4 are regulated by protein-protein interaction in stem cells.
OCT4（也称为 Oct3 和 Oct3/4），由 Pou5f1 编码，在早期胚胎细胞中表达，在早期发育、多能性维持和胚胎干细胞自我更新中发挥重要作用。它还调节体细胞重编程为诱导多能干细胞。有报道称，几种 OCT4 结合蛋白，包括 SOX2 和 NANOG，调节干细胞中的基因转录。越来越多的证据表明，不仅基因转录，而且 OCT4 的翻译后修饰在调节 OCT4 的表达和活性方面也起着关键作用。例如，泛素化和 SUMO 化已被报道调节 OCT4 蛋白稳定性。此外，OCT4 中 Ser347 的磷酸化也稳定了 OCT4 蛋白水平。最近，我们鉴定了 KAP1 作为 OCT4 结合蛋白，并报道了 KAP1 介导的 OCT4 蛋白稳定性调节。KAP1 的过表达导致小鼠胚胎干细胞增殖增加，并促进体细胞重编程，导致诱导多能干细胞。在这篇综述中，我们讨论了蛋白质 - 蛋白质相互作用如何调节干细胞中 OCT4 的蛋白稳定性和功能。
