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Journal Article

SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression


Guenther,  Stefan
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Schmitz, L., Dreute, J., Pfisterer, M., Guenther, S., Kracht, M., & Chillappagari, S. (2022). SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression. HELIYON, 8(3): e09029. doi:10.1016/j.heliyon.2022.e09029.

Cite as: https://hdl.handle.net/21.11116/0000-000A-ACEF-8
The functionally redundant ubiquitin E3 ligases SIAH1 and SIAH2 have been implicated in the regulation of metabolism and the hypoxic response, while their role in other signal-mediated processes such inflammatory gene expression remains to be defined. Here we have downregulated the expression of both SIAH proteins with specific siRNAs and investigated the functional consequences for IL-1 alpha-induced gene expression. The knockdown of SIAH1/2 modulated the expression of approximately one third of IL-1 alpha-regulated genes. These effects were not due to changes in the NF-kappa B and MAPK signaling pathways and rather employed further processes including those mediated by the coactivator p300. Most of the proteins encoded by SIAH1/2-regulated genes form a regulatory network of proinflammatory factors. Thus SIAH1/2 proteins function as variable rheostats that control the amplitude rather than the principal activation of the inflammatory gene response.