OLIG2

What is OLIG2 protein?

OLIG2 (oligodendrocyte transcription factor 2) gene is a protein coding gene which situated on the long arm of chromosome 21 at locus 21q22. OLIG2 is a transcription factor in the basic helix-loop-helix (bHLH) domain. OLIG2 protein is expressed in a variety of cell types, especially in the nervous system, including oligodendrocytes, some neurons and neural precursor cells. It plays a key role in the development and function of the central nervous system (CNS). OLIG2 is a key regulator of oligodendrocyte development, which is involved in regulating the differentiation, maturation and function of these cells. OLIG2 is essential for maintaining normal nerve conduction velocity and nerve signaling by activating gene expression associated with myelination. The OLIG2 protein is consisted of 323 amino acids and its molecular mass is approximately 32.4 kDa.

What is the function of OLIG2 protein?

OLIG2 is a key factor regulating the differentiation and maturation of oligodendrocytes. Oligodendrocytes are cells in the central nervous system that form myelin sheath, which is essential for the effective conduction of nerve signals. OLIG2 promotes the production and function of oligodendrocytes by activating specific gene programs. During the development of the nervous system, OLIG2 is involved in determining the fate of neural precursor cells, particularly in specifying that these cells become oligodendrocytes or specific types of neurons. Studies have shown that OLIG2 also plays a role in neuroprotection and repair processes in the adult brain.

OLIG2 Related Signaling Pathway

OLIG2 interacts with Notch signaling pathway. Notch signaling pathway plays an important role in maintaining the undifferentiated state of OPCs, and OLIG2 can regulate the activity of Notch signaling pathway, thereby affecting the self-renewal and differentiation of OPCs. OLIG2 can promote the proliferation and survival of oligodendrocyte precursor cells by activating the PI3K/Akt signaling pathway. OLIG2 is involved in regulating cell cycle progression and influencing the proliferation and differentiation of OPCs.

Fig1. Model of Olig2 phosphorylation-dependent glioma invasion. (Shiv K Singh, 2016)

OLIG2 Related Diseases

Mutations or abnormal expression of the OLIG2 gene have been associated with a variety of neurological diseases, including: Mutations in the OLIG2 gene are closely associated with the occurrence of Multiple Sclerosis (MS). In patients with MS, OLIG2 expression levels are often reduced. The mutation of OLIG2 gene is also one of the important factors in the development of brain glioma. OLIG2 expression levels are generally elevated and are associated with tumor prognosis. Spinocerebellar Ataxia (SCA) is a genetic disorder associated with mutations in the OLIG2 gene. In patients with SCA, OLIG2 expression levels are often reduced. Mutations in the OLIG2 gene have also been linked to other neurological disorders, such as Spinal Muscular Atrophy (SMA) and Huntington's Disease.

Bioapplications of OLIG2

The study of the function and expression patterns of OLIG2 could contribute to the development of new biomedical products, such as drugs for the treatment of neurodegenerative diseases or for promoting nerve regeneration. OLIG2 is a transcription factor, and its regulation of downstream effectors may be a potential target for gene therapy. With further research, practical therapeutic targeting of OLIG2 may be applied in the future. OLIG2 plays a role in the fate determination of neural precursor cells, which makes it of great value in stem cell research and potential stem cell therapeutic applications.

Case Study 1: Zhenhua Xu, 2022

Patients with MYC-amplified medulloblastoma (MB) have poor prognosis and frequently develop recurrence, thus new therapeutic approaches to prevent recurrence are needed. The researchers evaluated OLIG2 expression in a panel of mouse Myc-driven MB tumors, patient MB samples, and patient-derived xenograft (PDX) tumors and analyzed radiation sensitivity in OLIG2-high and OLIG2-low tumors in PDX lines. They assessed the effect of inhibition of OLIG2 by OLIG2-CRISPR or the small molecule inhibitor CT-179 combined with radiotherapy on tumor progression in PDX models. The results showed that MYC-associated MB can be stratified into OLIG2-high and OLIG2-low tumors based on OLIG2 protein expression. In MYC-amplified MB PDX models, OLIG2-low tumors were sensitive to radiation and rarely relapsed, whereas OLIG2-high tumors were resistant to radiation and consistently developed recurrence. In OLIG2-high tumors, irradiation eliminated the bulk of tumor cells; however, a small number of tumor cells comprising OLIG2- tumor cells and rare OLIG2+ tumor cells remained in the cerebellar tumor bed when examined immediately post-irradiation. The relapsed tumors mirrored the cellular composition of the primary tumors with enriched OLIG2 expression. Further studies demonstrated that OLIG2 was essential for recurrence, as OLIG2 disruption with CRISPR-mediated deletion or with the small molecule inhibitor CT-179 prevented recurrence from the residual radioresistant tumor cells.

Fig1. Western blot analysis of OLIG2 and MYC expression in six mouse MYC-driven MB tumors.

Fig2. Western blot analysis of OLIG2 and MYC expression in primary tumors, spontaneously relapsed tumors, and post-irradiation neurosphere-derived tumors.

Case Study 2: Ji Eun Lee, 2021

Oligodendrocyte transcription factor2 (Olig2) is a basic helix-loop-helix transcription factor that is expressed in the central nervous system during embryonic development. Olig2 is overexpressed in various malignant cell lines such as lung carcinoma, glioma and melanoma. Olig2 is known as a key transcription factor that promotes tumor growth in malignant glioma. However, the role of Olig2 in melanoma is not well characterized. This study analyzed the role of Olig2 in apoptosis, migration, and invasion of melanoma cells. The results confirmed that Olig2 was overexpressed in melanoma cells and tissues. Reduction of Olig2 increased apoptosis in melanoma cells by increasing p53 level and caspase-3/-7 enzyme activity. In addition, downregulation of Olig2 suppressed migration and invasion of melanoma cells by inhibiting EMT. Reduction of Olig2 inhibited expression of MMP-1 and the enzyme activity of MMP-2/-9 induced by TGF-β. Moreover, Olig2 was involved in the downstream stages of MEK/ERK and PI3K/AKT, which are major signaling pathways in metastatic progression of melanoma.

Fig3. Western blot analysis of Olig2 protein expression was performed with Olig2 (H-10) antibody.

Fig4. Olig2 regulated the EMT markers in melanoma cells.

OLIG2 has several biochemical functions, for example, DNA binding,HMG box domain binding,protein homodimerization activity. Some of the functions are cooperated with other proteins, some of the functions could acted by OLIG2 itself. We selected most functions OLIG2 had, and list some proteins which have the same functions with OLIG2. You can find most of the proteins on our site.

OLIG2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with OLIG2 here. Most of them are supplied by our site. Hope this information will be useful for your research of OLIG2.