How CBX proteins regulate normal and leukemic blood cells.

Autor: de Groot AP; European Research Institute for Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), The Netherlands.; Sanquin Research, Landsteiner Laboratory, Sanquin Blood Supply, Amsterdam, The Netherlands., de Haan G; European Research Institute for Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), The Netherlands.; Sanquin Research, Landsteiner Laboratory, Sanquin Blood Supply, Amsterdam, The Netherlands.; Department of Hematology, Amsterdam UMC, University of Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2024 Nov; Vol. 598 (22), pp. 2788-2806. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1002/1873-3468.14839
Abstrakt: Hematopoietic stem cell (HSC) fate decisions are dictated by epigenetic landscapes. The Polycomb Repressive Complex 1 (PRC1) represses genes that induce differentiation, thereby maintaining HSC self-renewal. Depending on which chromobox (CBX) protein (CBX2, CBX4, CBX6, CBX7, or CBX8) is part of the PRC1 complex, HSC fate decisions differ. Here, we review how this occurs. We describe how CBX proteins dictate age-related changes in HSCs and stimulate oncogenic HSC fate decisions, either as canonical PRC1 members or by alternative interactions, including non-epigenetic regulation. CBX2, CBX7, and CBX8 enhance leukemia progression. To target, reprogram, and kill leukemic cells, we suggest and describe multiple therapeutic strategies to interfere with the epigenetic functions of oncogenic CBX proteins. Future studies should clarify to what extent the non-epigenetic function of cytoplasmic CBX proteins is important for normal, aged, and leukemic blood cells.
(© 2024 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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