PMID:23857586

Citation	Wang, C, Liu, X, Liu, Y, Zhang, Q, Yao, Z, Huang, B, Zhang, P, Li, N and Cao, X (2013) Zinc Finger Protein 64 Promotes Toll-like Receptor-triggered Proinflammatory and Type I Interferon Production in Macrophages by Enhancing p65 Subunit Activation. J. Biol. Chem. 288:24600-8
Abstract	The molecular mechanisms that fine-tune the Toll-like receptor (TLR)-triggered innate immune response need further investigation. As an important transcription factor, zinc finger proteins (ZFPs) play important roles in many cell functions, including development, differentiation, tumorigenesis, and functions of the immune system. However, the role of ZFP members in the innate immune responses remains unclear. Here we showed that the expression of C2H2-type ZFP, ZFP64, was significantly up-regulated in macrophages upon stimulation with TLR ligands, including LPS, CpG oligodeoxynucleotides, or poly(I:C). ZFP64 overexpression promoted TLR-triggered TNF-α, IL-6, and IFN-β production in macrophages. Coincidently, knockdown of ZFP64 expression significantly inhibited the production of the above cytokines. However, activation of MAPK and IRF3 was not responsible for the ZFP64-mediated promotion of cytokine production. Interestingly, ZFP64 significantly up-regulated TLR-induced NF-κB activation. ZFP64 could bind to the promoter of the TNF-α, IL-6, and IFN-β genes in macrophages only after TLR ligation. Furthermore, ZFP64 associated with the NF-κB p65 subunit upon LPS stimulation, and TLR-ligated macrophages showed a lower level of p65 recruitment to the TNF-α, IL-6, and IFN-β gene promoter in the absence of ZFP64. The data identify ZFP64 as a downstream positive regulator of TLR-initiated innate immune responses by associating with the NF-κB p65 subunit, enhancing p65 recruitment to the target gene promoters and increasing p65 activation and, thus, leading to the promotion of TLR-triggered proinflammatory cytokine and type I interferon production. Our findings add mechanistic insight into the efficient activation of the TLR innate response against invading pathogens.
Links	PubMed PMC3750158 Online version:10.1074/jbc.M113.473397
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ZFP64	involved_in	GO:0032760: positive regulation of tumor necrosis factor production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZFP64	involved_in	GO:0032760: positive regulation of tumor necrosis factor production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZFP64	involved_in	GO:0032755: positive regulation of interleukin-6 production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZFP64	involved_in	GO:0032755: positive regulation of interleukin-6 production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZFP64	involved_in	GO:0032728: positive regulation of interferon-beta production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZFP64	involved_in	GO:0032728: positive regulation of interferon-beta production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ZFP64		GO:0032760: positive regulation of tumor necrosis factor production	ECO:0000314:		P		The overexpression of ZFP64 and stimulated with LPS resulted in increased amounts of Tumor necrosis Factor production alpha as shown in Figure 2 A graph 1 elisa indicating that ZFP64 is a positive regulator of tumor necrosis factor production in RAW264.7 cells.	complete CACAO 8786
MOUSE:ZFP64		GO:0032760: positive regulation of tumor necrosis factor production	ECO:0000315:		P		In mouse macrophages siRNA was used to decrease ZFP64 production thus resulting in Figure 2B graph 1 showing with stimulation by LPS decreased amounts of Tumor Necrosis Factor Alpha is made thus showing that ZFP64 when present is a positive regulator of tumor necrosis factor alpha production.	complete CACAO 8787
MOUSE:ZFP64		GO:0032755: positive regulation of interleukin-6 production	ECO:0000314:		P		Elisa after overexpression of ZFP64 in RAW264.7 cells shows in figure 2A graph 2 that interleukin-6 (IL-6) production has been increased from the normal Raw264.7 cells indicating ZFP64 positively regulates interleukin-6 production.	complete CACAO 8789
MOUSE:ZFP64		GO:0032755: positive regulation of interleukin-6 production	ECO:0000315:		P		Elisa was run after using siRNA to decrease expression of ZFP64 resulting in Figure 2B graph 2 showing decreased expression of Interleukin-6 indicating that ZFP64 positively regulates Interleukin-6 production.	complete CACAO 8790
MOUSE:ZFP64		GO:0032728: positive regulation of interferon-beta production	ECO:0000314:		P		Figure 2A graph 3 of ELISA shows when ZFP64 is overexpressed, interferon beta production increases thus indicating that ZFP64 positively regulates interferon-beta production inRAW264.7 cells.	complete CACAO 8791
MOUSE:ZFP64		GO:0032728: positive regulation of interferon-beta production	ECO:0000315:		P		In figure 2B graph 3 elisa when siRNA was insereted to decrease ZFP64 expression shows that interferon-beta production decreases indicating that ZFP64 positively regulates interferon-beta production.	complete CACAO 8792

References

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