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泛素化调控增殖细胞中OCT-3/4的细胞功能

Cellular Functions of OCT-3/4 Regulated by Ubiquitination in Proliferating Cells.

作者信息

Baek Kwang-Hyun, Choi Jihye, Pei Chang-Zhu

机构信息

Department of Biomedical Science, CHA University, Gyeonggi-Do 13488, Korea.

出版信息

Cancers (Basel). 2020 Mar 12;12(3):663. doi: 10.3390/cancers12030663.

Abstract

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.

摘要

八聚体结合转录因子3/4(OCT-3/4)参与体细胞癌的肿瘤发生,在癌症发展过程中具有多种功能。在各种人类体细胞肿瘤中均检测到OCT-3/4的过表达,这表明OCT-3/4的激活可能促进癌症的发生和发展。干细胞在至少四种转录因子,即OCT-3/4、含SRY盒基因2(SOX2)、Krüppel样因子4(KLF4)和c-MYC的帮助下,可以进行自我更新、多能性和重编程。其中,OCT-3/4在维持胚胎干细胞(ESC)的未分化状态以及诱导多能干细胞(iPSC)的产生中起关键作用。干细胞可以通过有丝分裂进行分裂并分化为特定的细胞类型,即三个胚胎胚层:内胚层、中胚层和滋养外胚层。已经证明,OCT-3/4的稳定性由泛素-蛋白酶体系统(UPS)介导,这是细胞内稳态的关键细胞机制之一。该机制的框架很简单,但蛋白水解机制很复杂。泛素化促进蛋白质降解,OCT-3/4的泛素化导致细胞增殖和分化的调节。因此,预计OCT-3/4可能在增殖细胞的增殖和分化中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a11/7139964/06b0d9c1485f/cancers-12-00663-g001.jpg

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