SIKE1 Human
Description
Biological Function and Mechanism
SIKE1 Human acts as a negative regulator of interferon and inflammatory pathways, primarily through interactions with kinases and adaptors:
Key Interactions and Pathways
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IKK-ε and TBK1: Directly binds to these kinases to inhibit TLR3- and virus-mediated interferon responses .
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TLR3 Signaling: Disrupts interactions between TBK1/IKK-ε and TICAM1/TRIF, IRF3, and RIG-I, blocking ISRE/IFN-β activation .
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NF-κB Pathways: No inhibition observed, distinguishing its role from broader immune suppression .
Role in Cardiac Hypertrophy
A landmark study in Nature Communications demonstrated that SIKE1 suppresses pathological cardiac remodeling via the TBK1-AKT axis :
Mechanistically, SIKE1 binds TBK1’s C-terminal domain (aa 384–729), inhibiting its kinase activity and downstream AKT phosphorylation .
Research Applications and Techniques
SIKE1 Human is employed in diverse experimental systems:
Experimental Models
Key Techniques
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STRIPAK Complex Studies: Link SIKE1 to striatin-interacting phosphatase/kinase (STRIPAK) complexes, regulating Hippo signaling .
Interaction Network and Functional Partners
SIKE1 Human interacts with proteins involved in cytoskeletal organization and signaling:
These interactions suggest SIKE1’s role in cellular architecture and stress response pathways .
Conservation Across Species
SIKE1 is evolutionarily conserved, with orthologs identified in:
| Species | Genomic Location | Key Features | Reference |
|---|---|---|---|
| Human | Chromosome 1 | Cardiac hypertrophy regulation | |
| Mouse | Chromosome 3 (Chr3) | Cardiac remodeling studies | |
| Zebrafish | Chromosome 23 | Orthologous to human SIKE1 (ZFIN) |
Clinical and Therapeutic Implications
SIKE1’s inhibition of TBK1-AKT signaling positions it as a potential therapeutic target for:
Product Specs
Product Science Overview
SIKE1 was first identified through yeast two-hybrid screening of a human B-cell cDNA library using full-length IKK-epsilon (IKBKE) as bait . The protein consists of 207 amino acids and contains two coiled-coil motifs . Northern blot analysis revealed that SIKE1 is ubiquitously expressed, with strong expression in the brain, heart, kidney, and placenta, moderate expression in the liver and small intestine, and weak expression in skeletal muscle, colon, thymus, spleen, lung, and leukocytes .
SIKE1 interacts with IKK-epsilon (IKBKE) and TBK1 (TANK-binding kinase 1) and acts as a suppressor of TLR3 (Toll-like receptor 3) and virus-triggered interferon activation pathways . It specifically inhibits the activation of interferon-stimulated regulatory elements (ISRE) and the IFN-beta promoter mediated by IKK-epsilon and TBK1 . This inhibition occurs through the disruption of interactions between IKK-epsilon or TBK1 and other proteins such as TRIF (TIR-domain-containing adapter-inducing interferon-β) and IRF3 (interferon regulatory factor 3) .
Under physiological conditions, SIKE1 associates with TBK1 but dissociates upon viral infection or TLR3 activation . This dissociation allows TBK1 to interact with other proteins and activate the interferon response. SIKE1’s role as an inhibitor is crucial for preventing excessive activation of the immune response, which could lead to inflammation and tissue damage .
Recombinant human SIKE1 is produced for research purposes to study its function and potential therapeutic applications. It is typically expressed in bacterial or mammalian expression systems and purified for use in various assays . The recombinant protein is used to investigate the molecular mechanisms of immune regulation and to develop potential treatments for diseases involving dysregulated immune responses .
Research on SIKE1 has provided insights into its role in immune regulation and its potential as a therapeutic target. Studies have shown that knockdown of SIKE1 expression potentiates poly(I:C)- and virus-induced activation of ISRE and the IFN-beta promoter, whereas overexpression of SIKE1 inhibits these responses . This suggests that modulating SIKE1 levels could be a strategy for controlling immune responses in various diseases .
