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.
Highlights
Since octamer-binding transcription factor 3/4 (OCT-3/4) was first identified about 30 years ago, it has been extensively studied from many different aspects as an important transcription factor.OCT-3/4 is a core transcription factor that maintains pluripotency and controls development of early mammalian embryos [1]
posttranslational modifications (PTMs) of OCT-3/4 regulate cellular pluripotency through several mechanisms including phosphorylation [73], SUMOylation [74], ubiquitination [49], glycosylation [38], methylation [40], and acetylation [42], which are important for OCT-3/4 functions
We summarize interesting findings regarding ubiquitination of OCT-3/4, which is related to differentiation and proliferation in proliferating cells
Summary
Since octamer-binding transcription factor 3/4 (OCT-3/4) was first identified about 30 years ago, it has been extensively studied from many different aspects as an important transcription factor. OCT-3/4 is an important transcription factor that maintains the pluripotency and self-renewal of ESCs. Wang et al recently found that some stem cell-associated transcription factors, such as OCT-3/4, SOX2, NANOG, and KLF4, are related to the tumorigenesis of somatic cancers [3]. High risk human papillomavirus (HR-HPV) promotes self-renewal by upregulating OCT-3/4, NANOG, and SOX2 expression to maintain the cervical cancer stem cell (CCSC) in the cervical cancer [62]. 293T cells, while knockdown of Itch reduces OCT-3/4 transcriptional activity in ESCs. In addition, Itch directly interacts with and ubiquitinates OCT-3/4 protein through K63-linked polyubiquitination to promote OCT-4 degradation, and increased OCT-3/4 transcriptional activity is counterbalanced by degradation of OCT-3/4 mediated by E3 ligase function of Itch [50]. Ring1A/B (Ring1/Rnf2)-mediated polycomb silencing functions downstream of the core transcriptional regulatory circuitry to retain the characteristics of ESCs. [72]
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