Related Experiment Video
Updated: Sep 30, 2025

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells
Published on: May 24, 2014
SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression
M Lienhard Schmitz1, Jan Dreute1, Maximilian Pfisterer1
1Institute of Biochemistry, Justus-Liebig-University, D-35392, Giessen, Germany.
Abstract:
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.
Related Concept Videos
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
Gene Regulation in Microbial Communities: Quorum Sensing
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The JAK-STAT Signaling Pathway
TGF - β Signaling Pathway

