TNAP, a Novel Repressor of NF-κB-inducing Kinase, Suppresses NF-κB Activation

Hu, Wen; Mo, Xian Ming; Walters, Winston; Brambilla, Roberta; Bethea, John R.

doi:10.1074/jbc.m405699200

Cited by 33 publications

(31 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRAF3 (36) and TRAF2 (37)). In addition, several novel clones were identified, one of which, TNAP, is a negative regulator of cytokine-induced NF-B activation (26). In the present study we report the identification of a 211-amino acid C-terminal portion of a novel protein, NIBP.…”

Section: Resultsmentioning

confidence: 66%

“…The bait, encoding the N-terminal domain (amino acids 1-145) of NIK, was inserted into the GAL4 DNA binding domain in the yeast expression vector pBridge (Clontech) as previously described (26). The yeast strain G1945 was transformed with pBridge-NIK followed by the pACT2 expression vector that contained a human brain cDNA library fused to the GAL4 transactivation domain.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

NIBP, a Novel NIK and IKKβ-binding Protein That Enhances NF-κB Activation

Pendergast

et al. 2005

Journal of Biological Chemistry

Self Cite

118

168

View full text Add to dashboard Cite

The transcription factor NF-B plays an important role in both physiological and pathological events in the central nervous system. Nevertheless, the mechanisms of NF-B-mediated regulation of gene expression, and the signaling molecules participating in the NF-B pathway in the central nervous system are, to date, poorly understood. To identify such molecules, we conducted a yeast two-hybrid screen of a human brain cDNA library using NIK as bait. As a result, we identified a novel NIK and IKK␤ binding protein designated NIBP that is mainly expressed in brain, muscle, heart, and kidney. Interestingly, low levels of expression were detected in immune tissues such as spleen, thymus, and peripheral blood leukocytes, where NF-B is known to modulate immune function. We demonstrated by immunohistochemistry that NIBP expression in the brain is localized to neurons. NIBP physically interacts with NIK, IKK␤, but not IKK␣ or IKK␥. NIBP overexpression potentiates tumor necrosis factor-␣-induced NF-B activation through increased phosphorylation of the IKK complex and its downstream IB␣ and p65 substrates. Finally, knockdown of NIBP expression by small interfering RNA reduces tumor necrosis factor-␣-induced NF-B activation, prevents nerve growth factor-induced neuronal differentiation, and decreases Bcl-xL gene expression in PC12 cells. Our data demonstrate that NIBP, by interacting with NIK and IKK␤, is a new enhancer of the cytokine-induced NF-B signaling pathway. Because of its neuronal expression, we propose that NIBP may be a potential target for modulating the NF-B signaling cascade in neuronal pathologies dependent upon abnormal activation of this pathway.

show abstract

Section: Resultsmentioning

confidence: 66%

Section: Methodsmentioning

confidence: 99%

NIBP, a Novel NIK and IKKβ-binding Protein That Enhances NF-κB Activation

Pendergast

et al. 2005

Journal of Biological Chemistry

Self Cite

118

168

View full text Add to dashboard Cite

show abstract

“…These multiprotein interactions have been partially mapped to the NIK molecule. The NH 2 terminus of NIK binds TRAF3 and TNAP (38,39), whereas the COOH terminus is known to interact with TRAF2 (amino acids 624 -947 of NIK) and IKK␣ (amino acids 735-947 of NIK) (35)(36)(37). Our deletion experiments indicate that the NIK COOH terminus (amino acids 660 -947) is also required for MAVS interaction.…”

Section: Discussionmentioning

confidence: 70%

“…NIK is a serine-threonine kinase of the mitogen-activated MAP kinase family known to associate with the TNF receptor-associated factors (TRAFs)-2, and 3, the TRAF-and NIK-associated factor (TNAP), and the IKK␣ kinase (35)(36)(37)(38)(39). TRAF association allows NIK to couple with activated receptors in the TNF superfamily.…”

Section: Discussionmentioning

confidence: 99%

Respiratory Syncytial Virus Induces RelA Release from Cytoplasmic 100-kDa NF-κB2 Complexes via a Novel Retinoic Acid-inducible Gene-I·NF-κB-inducing Kinase Signaling Pathway

Liu

Garofalo

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) is a primary cause of severe lower respiratory tract infection in children worldwide. RSV infects airway epithelial cells, where it activates inflammatory genes via the NF-B pathway. NF-B is controlled by two pathways, a canonical pathway that releases sequestered RelA complexes from the IB␣ inhibitor, and a second, the noncanonical pathway, that releases RelB from the 100-kDa NF-B2 complex. Recently we found that the retinoic acid-inducible gene I (RIG-I) is a major intracellular RSV sensor upstream of the canonical pathway. In this study, we surprisingly found that RIG-I silencing also inhibited p100 processing to 52-kDa NF-B2 ("p52"), suggesting that RIG-I was functionally upstream of the noncanonical regulatory kinase complex composed of NIK⅐IKK␣ subunits. Co-immunoprecipitation experiments not only demonstrated that NIK associated with RIG-I and its downstream adaptor, mitochondrial antiviral signaling (MAVS), but also showed the association between IKK␣ and MAVS. To further understand the role of the NIK⅐IKK␣ pathway, we compared RSV-induced NF-B activation using wild type, Ikk␥ ؊/؊

show abstract

“…One potential negative regulator of NIK is TRAF-and NIK-associated protein (TNAP), which was identified by yeast two-hybrid screen of an adult human brain cDNA library using NIK as bait [79]. The isolated TNAP clone encodes the C-terminal 140 amino acids of a truncated protein.…”

Section: Nik Regulatorsmentioning

confidence: 99%

Non-canonical NF-κB signaling pathway

2010

View full text Add to dashboard Cite

The non-canonical NF-κB pathway is an important arm of NF-κB signaling that predominantly targets activation of the p52/RelB NF-κB complex. This pathway depends on the inducible processing of p100, a molecule functioning as both the precursor of p52 and a RelB-specific inhibitor. A central signaling component of the non-canonical pathway is NF-κB-inducing kinase (NIK), which integrates signals from a subset of TNF receptor family members and activates a downstream kinase, IκB kinase-α (IKKα), for triggering p100 phosphorylation and processing. A unique mechanism of NIK regulation is through its fate control: the basal level of NIK is kept low by a TRAF-cIAP destruction complex and signal-induced non-canonical NF-κB signaling involves NIK stabilization. Tight control of the fate of NIK is important, since deregulated NIK accumulation is associated with lymphoid malignancies.

show abstract

TNAP, a Novel Repressor of NF-κB-inducing Kinase, Suppresses NF-κB Activation

Cited by 33 publications

References 96 publications

NIBP, a Novel NIK and IKKβ-binding Protein That Enhances NF-κB Activation

NIBP, a Novel NIK and IKKβ-binding Protein That Enhances NF-κB Activation

Respiratory Syncytial Virus Induces RelA Release from Cytoplasmic 100-kDa NF-κB2 Complexes via a Novel Retinoic Acid-inducible Gene-I·NF-κB-inducing Kinase Signaling Pathway

Non-canonical NF-κB signaling pathway

Contact Info

Product

Resources

About