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GSK3 Kinase Inhibitor, CHIR, Suppress Transcription of Tissue Specific POU2F1 Isoform in Burkitt Namalwa Lymphoma Cells

Authors
  • Pankratova, E. V.1
  • Portseva, T. N.1
  • Makarova, A. A.1
  • Ilyin, Yu. V.1
  • Stepchenko, A. G.1
  • Georgieva, S. G.1
  • 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia , Moscow (Russia)
Type
Published Article
Journal
Doklady Biochemistry and Biophysics
Publisher
Pleiades Publishing
Publication Date
Mar 10, 2021
Volume
496
Issue
1
Pages
32–35
Identifiers
DOI: 10.1134/S1607672921010087
Source
Springer Nature
Keywords
License
Green

Abstract

AbstractPOU2F1 (Oct-1) is a transcription factor, the overexpression of which is found in many human malignant tumors; a significant increase in its level in cells determines the malignant potential of the tumor. POU2F1 is represented in cells by several isoforms that are transcribed from alternative promoters. In Burkitt’s B-cell lymphoma Namalwa, the concentration of tissue-specific isoform Oct-1L is several times higher than in normal B cells. We tested the potential to inhibit the transcription of individual Oct-1 isoforms using the GSK3 kinase inhibitor CHIR, an aminopyrimidine derivative. We have shown that CHIR specifically affects the expression of the tissue-specific isoform Oct-1L, significantly reducing the level of mRNA and Oct-1L protein. However, CHIR does not change the amount of mRNA and protein of the ubiquitous isoform Oct-1A in Namalwa tumor cells. The results obtained show that it is possible to develop a system for selective inhibition of Oct-1 transcription factor isoforms in human cells to suppress drug resistance of tumor cells with a high POU2F1 content.

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