SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression

Autor: M. Lienhard Schmitz, Jan Dreute, Maximilian Pfisterer, Stefan Günther, Michael Kracht, Shashipavan Chillappagari
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Heliyon, Vol 8, Iss 3, Pp e09029- (2022)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2022.e09029
Popis: 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-1α-induced gene expression. The knockdown of SIAH1/2 modulated the expression of approximately one third of IL-1α-regulated genes. These effects were not due to changes in the NF-κB 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.
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