Molecules and Cells

  • 제44권7호
  • /
  • Pages.444-457
  • /
  • 2021
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  • 1016-8478(pISSN)
  • /
  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis

  • Kim, Hyun Jeong (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Park, Jin Woo (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Kang, Joo-Young (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Seo, Sang-Beom (Department of Life Science, College of Natural Sciences, Chung-Ang University)
  • 투고 : 2021.01.15
  • 심사 : 2021.04.29
  • 발행 : 2021.07.31
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초록

Although the mechanism of chronic myeloid leukemia (CML) initiation through BCR/ABL oncogene has been well characterized, CML cell differentiation into erythroid lineage cells remains poorly understood. Using CRISPR-Cas9 screening, we identify Chromobox 8 (CBX8) as a negative regulator of K562 cell differentiation into erythrocytes. CBX8 is degraded via proteasomal pathway during K562 cell differentiation, which activates the expression of erythroid differentiation-related genes that are repressed by CBX8 in the complex of PRC1. During the differentiation process, the serine/threonine-protein kinase PIM1 phosphorylates serine 196 on CBX8, which contributes to CBX8 reduction. When CD235A expression levels are analyzed, the result reveals that the knockdown of PIM1 inhibits K562 cell differentiation. We also identify TRIM28 as another interaction partner of CBX8 by proteomic analysis. Intriguingly, TRIM28 maintains protein stability of CBX8 and TRIM28 loss significantly induces proteasomal degradation of CBX8, resulting in an acceleration of erythroid differentiation. Here, we demonstrate the involvement of the CBX8-TRIM28 axis during CML cell differentiation, suggesting that CBX8 and TRIM28 are promising novel targets for CML research.

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과제정보

This research was supported by the Chung-Ang University Graduate Research Scholarship in 2019 and by the Basic Science Research program through the National Research Foundation of Korea (NRF-2020R1F1A1064241).

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