The regulatory interplay between Oct-1 isoforms contributes to hematopoiesis and the isoforms imbalance correlates with a malignant transformation of B cells
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Elizaveta V. Pankratova1,*, Alexander G. Stepchenko1,*, Irina D. Krylova1, Tatiana N. Portseva1,2 and Sofia G. Georgieva1
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
2Pirogov Russian National Research Medical University, Moscow, Russia
*These authors have contributed equally to the work
Sofia G. Georgieva, email: firstname.lastname@example.org
Elizaveta V. Pankratova, email: email@example.com
Keywords: POU2F1; isoforms; hematopoietic cells differentiation; molecular therapeutic target
Abbreviations: POU2F1, POU domain class 2 transcription factor 1
Received: April 01, 2018 Accepted: May 31, 2018 Published: July 06, 2018
Oct-1(POU2F1) is a DNA-binding transcription regulator and its level being highly increased in many human cancers. Oct-1 is present in the human cells as a family of functionally different isoforms which are transcribed from alternative promoters. Here, we have demonstrated that expression patterns of Oct-1 isoforms change during differentiation of hematopoetic progenitor cells (CD34+) (HPCs) to the B (CD19+) and T (CD3+) cells. While Oct-1L is expressed at a high level in the CD34+ HPCs, its expression level drops dramatically during the T-cell differentiation, although remains nearly the same in B-cells. We have described the novel human Oct-1R isoform which is conserved in mammals and is B cell-specific. Oct-1R was found in B cells, but not in HPCs. Oct-1R is transcribed from the same promoter as Oct-1L, another lymphocyte-specific isoform. Overexpression of Oct-1R and Oct-1L in the Namalwa cells leads to the repression of many genes involved in B-lymphocyte differentiation and signal transduction. Thus these isoforms may regulate the particular stages of development of normal B cells and maintain their proper differentiation status. However the extremely high level of Oct-1L isoform observed in the B-lymphoblast tumor cell lines indicated that the excess of Oct-L seem likely to considerably decrease the differentiation ability of these cells. Oct-1 may serve as a therapeutic target for many tumors, but it should be noted that in a tumor the content of a certain isoform Oct-1, rather than the total Oct-1 protein, can be increased.
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