Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axisopen access
- Authors
- Kim ,Hyun Jeong; Park, Jin Woo; Kang, Joo-Young; Seo, Sang-Beom
- Issue Date
- Jul-2021
- Publisher
- 한국분자세포생물학회
- Keywords
- chromobox8; chronic myeloid leukemia; erythroid differentiation; serine/threonine-protein kinase pim-1; tripartite motif containing 28
- Citation
- Molecules and Cells, v.44, no.7, pp 444 - 457
- Pages
- 14
- Journal Title
- Molecules and Cells
- Volume
- 44
- Number
- 7
- Start Page
- 444
- End Page
- 457
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/49280
- DOI
- 10.14348/molcells.2021.0012
- ISSN
- 1016-8478
0219-1032
- Abstract
- 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.
- Files in This Item
-
- Appears in
Collections - College of Natural Sciences > Department of Life Science > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/49280)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.