Histone deacetylase 7 activates 6-phosphogluconate dehydrogenase via an enzyme-independent mechanism that involves the N-terminal protein-protein interaction domain.

Autor:	Wang Y; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia., Curson JEB; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia., Ramnath D; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia., Das Gupta K; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia., Reid RC; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia., Karunakaran D; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland 4072, Australia.; Victorian Heart Institute, Victorian Heart Hospital, Clayton, Victoria 3168, Australia.; Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia., Fairlie DP; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.; ARC Centre of Excellence for Innovations in Peptide and Protein Science, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia., Sweet MJ; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2024 Nov 06; Vol. 481 (21), pp. 1569-1584.
DOI:	10.1042/BCJ20240380
Abstrakt:	Histone deacetylase 7 (HDAC7) is a member of the class IIa family of classical HDACs with important roles in cell development, differentiation, and activation, including in macrophages and other innate immune cells. HDAC7 and other class IIa HDACs act as transcriptional repressors in the nucleus but, in some cell types, they can also act in the cytoplasm to modify non-nuclear proteins and/or scaffold signalling complexes. In macrophages, HDAC7 is a cytoplasmic protein with both pro- and anti-inflammatory functions, with the latter activity involving activation of the pentose phosphate pathway (PPP) enzyme 6-phosphogluconate dehydrogenase (6PGD) and the generation of anti-inflammatory metabolite ribulose-5-phosphate. Here, we used ectopic expression systems and biochemical approaches to investigate the mechanism by which HDAC7 promotes 6PGD enzyme activity. We reveal that HDAC7 enzyme activity is not required for its activation of 6PGD and that the N-terminal protein-protein interaction domain of HDAC7 is sufficient to initiate this response. Mechanistically, the N-terminus of HDAC7 increases the affinity of 6PGD for NADP+, promotes the generation of a shorter form of 6PGD, and enhances the formation of higher order protein complexes, implicating its scaffolding function in engagement of the PPP. This contrasts with the pro-inflammatory function of HDAC7 in macrophages, in which it promotes deacetylation of the glycolytic enzyme pyruvate kinase M2 for inflammatory cytokine production. (© 2024 The Author(s).)
Databáze:	MEDLINE
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