ArticleThe Journal of biological chemistry2014
Nuclear factor-κB-inducing kinase (NIK) contains an amino-terminal inhibitor of apoptosis (IAP)-binding motif (IBM) that potentiates NIK degradation by cellular IAP1 (c-IAP1).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Necroptosis triggers inflammatory interferon signatures in patient-derived metastatic breast cancer organoids.Signal transduction and targeted therapy · 2026Article
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- The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma.Nature communications · 2022Article
- Cellular inhibitor of apoptosis 2 (cIAP2) restricts neuroinflammation during experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2022Article
- Cytoplasmic and Nuclear Functions of cIAP1.Biomolecules · 2022Review
- Review
- Article
- A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas.Human molecular genetics · 2019Article
- Increased HMGB1 expression correlates with higher expression of c-IAP2 and pERK in colorectal cancer.Medicine · 2019Article
- Article
- The Many Roles of Ubiquitin in NF-κB Signaling.Biomedicines · 2018Review
- E2F1 binds to the peptide-binding groove within the BIR3 domain of cIAP1 and requires cIAP1 for chromatin binding.PloS one · 2018Article
- Recent advances in understanding inhibitor of apoptosis proteins.F1000Research · 2018Review
- [Effect of Circular RNA UBAP2 Silencing on Proliferation and Invasion of Human Lung Cancer A549 Cells and Its Mechanism].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2017Article
- Signalome-wide assessment of host cell response to hepatitis C virus.Nature communications · 2017Article
- Inducing death in tumor cells: roles of the inhibitor of apoptosis proteins.F1000Research · 2017Review
- Bivalent IAP antagonists, but not monovalent IAP antagonists, inhibit TNF-mediated NF-Cell death discovery · 2017Article
- San-Huang-Xie-Xin-Tang Constituents Exert Drug-Drug Interaction of Mutual Reinforcement at Both Pharmacodynamics and Pharmacokinetic Level: A Review.Frontiers in pharmacology · 2016Review
- SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells.Oncotarget · 2015Article
- The cnidarian origin of the proto-oncogenes NF-κB/STAT and WNT-like oncogenic pathway drives the ctenophores (Review).International journal of oncology · 2015Review
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4 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of the noncanonical NF-κB pathway hinges on the stability of the NF-κB-inducing kinase (NIK), which is kept at low levels basally by a protein complex consisting of the E3 ubiquitin ligases cellular inhibitor of apoptosis 1 and 2 (c-IAP1/2) proteins and the tumor necrosis factor receptor-associated factors 2 and 3 (TRAF2/3). NIK is brought into close proximity to the c-IAPs through a TRAF2-TRAF3 bridge where TRAF2 recruits c-IAP1/2 and TRAF3 binds to NIK. However, it is not clear how the c-IAPs specifically recognize and ubiquitylate NIK in the complex. We have identified an IAP-binding motif (IBM) at the amino terminus of NIK. IBMs are utilized by a number of proapoptotic proteins to antagonize IAP function. Here, we utilize mutational studies to demonstrate that wild-type NIK is destabilized in the presence of c-IAP1, whereas the NIK IBM mutant is stable. NIK interacts with the second baculovirus IAP repeat (BIR2) domain of c-IAP1 via the IBM, and this interaction, in turn, provides substrate recognition for c-IAP1 mediated ubiquitylation and degradation of NIK. Furthermore, in the presence of the NIK IBM mutant, we observed an elevated processing of p100 to p52 followed by increased expression of NF-κB target genes. Together, these findings reveal the novel identification and function of the NIK IBM, which promotes c-IAP1-dependent ubiquitylation of NIK, resulting in optimal NIK turnover to ensure that noncanonical NF-κB signaling is off in the absence of an activating signal.
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