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

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.

Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype

“…OCT-3/4 and NANOG regulate the self-renewal, proliferation, survival, and multi-lineage differentiation potential of ESCs. Moreover, these markers not only sustain pluripotency of undifferentiated ESCs but may also act as oncogenes since their overexpression has been identified in several cancers [ 45 , 46 ].…”

“…OCT-3/4 and NANOG regulate the self-renewal, proliferation, survival, and multi-lineage differentiation potential of ESCs. Moreover, these markers not only sustain pluripotency of undifferentiated ESCs but may also act as oncogenes since their overexpression has been identified in several cancers [45,46]. Deregulation of sex-determining region Y-Box (SOX) family genes encoding proteins that contribute to cell development, homeostasis, and regeneration [47] was also determined in sarcomas, including ChS.…”

Potential of Induced Pluripotent Stem Cells for Use in Gene Therapy: History, Molecular Bases, and Medical Perspectives

“…It has been documented that Oct3/4 codes a transcription factor containing the POU homeodomain. C-MYC codes for a nuclear phosphoprotein that controls the progression of the cell cycle [ 17 ]. Evidence has been reported that Oct3/4 and Sox2 are key transcriptional factors that inhibit the expression of genes associated with embryonal stem cell differentiation [ 18 ].…”

“…It has been demonstrated that ubiquitination promotes protein degradation and in the case of Oct3/4 leads to regulation of cellular proliferation and differentiation. Taking it into account, it may be concluded that this factor is not only responsible for cell proliferation but also for the control of their differentiation [ 17 ].…”

A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis

“…The abnormal expression of long non-coding RNA (lncRNA) and microRNA (miRNA) can be detected in almost all CRC tumor tissues 5 , 6 LncRNA and miRNA are closely related to the occurrence and development of tumor, and play a very important role of oncogene or tumor suppressor gene in the development of tumor by regulating tumor cell proliferation, invasion, apoptosis and drug resistance 7 , 8 A variety of lncRNAs are closely related to the occurrence and development of CRC; however, their function and mechanisms remain to be fully elucidated. SRY-box containing gene 2 (Sox2) is a key regulatory factor involving vertebrate cell stemness 9 . Sox2 overlapping transcript (SOX2OT) is a lncRNA located overlaps with the SOX2 gene in sequence 10 .…”