Neurodevelopmental functions and activities of the KAT3 class of lysine acetyltransferases.

Autor:	Shahib AK; Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada., Rastegar M; Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada., van Wijnen AJ; Department of Biochemistry, University of Vermont Larner College of Medicine, Burlington, VT, USA., Davie JR; Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada.; Paul Albrechtsen Research Institute, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada.
Jazyk:	angličtina
Zdroj:	Biochemistry and cell biology = Biochimie et biologie cellulaire [Biochem Cell Biol] 2024 Dec 01; Vol. 102 (6), pp. 430-447. Date of Electronic Publication: 2024 Sep 18.
DOI:	10.1139/bcb-2024-0156
Abstrakt:	The human lysine acetyltransferases KAT3A ( CREBBP ) and KAT3B ( EP300 ) are essential enzymes in gene regulation in the nucleus. Their ubiquitous expression in metazoan cell types controls cell proliferation and differentiation during development. This comprehensive review delves into the biological roles of KAT3A and KAT3B in neurodevelopment, shedding light on how alterations in their regulation or activity can potentially contribute to a spectrum of neurodegenerative diseases (e.g., Huntington's and Alzheimer's). We explore the pathophysiological implications of KAT3 function loss in these disorders, considering their conserved protein domains and biochemical functions in chromatin regulation. The discussion also underscores the crucial role of KAT3 proteins and their substrates in supporting the integration of key cell signaling pathways. Furthermore, the narrative highlights the interdependence of KAT3-mediated lysine acetylation with lysine methylation and arginine methylation. From a cellular perspective, KAT3-dependent signal integration at subnuclear domains is mediated by liquid-liquid phase separation in response to KAT3-mediated lysine acetylation. The disruption of these finely tuned regulatory processes underscores their pathological roles in neurodegeneration. This review also points to the exciting potential for future research in this field, inspiring further investigation and discovery in the area of neurodevelopment and neurodegenerative diseases. Competing Interests: The authors declare that they have no conflicts of interest.
Databáze:	MEDLINE
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