ReviewCell research2011
Regulation and function of TPL-2, an IκB kinase-regulated MAP kinase kinase kinase.
Review in Cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 92 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
92 citing papers in PubMed, 139 citations in OpenAlex.
- First-In-Human Evaluation of the Pharmacokinetics, Pharmacodynamics, and Safety of Tilpisertib Fosmecarbil (GS-5290), an Oral Prodrug of a Tumor Progression Locus 2 Inhibitor in Healthy Participants.Journal of clinical pharmacology · 2026Trial
- p38γ and p38δ MAP kinases in inflammation.Biochemical Society transactions · 2026Review
- MEK Inhibitors and Toll-like Receptor Signaling: Implications for Infection and Inflammation.International journal of molecular sciences · 2026Review
- Tim-3 agonist restrains ILC2 function and attenuates airway hyperreactivity via NLK pathway.Nature communications · 2026Article
- The ASFV CD2v protein inhibits apoptosis by inducing proteasomal degradation of BimJournal of virology · 2026Article
- ApCtf1β-Interacting Target Proteins BDPH1 and BDEUL12 Regulate Pathogenicity in Arthrinium phaeospermum.Molecular plant pathology · 2026Article
- PCSK9-Mediated Inflammation in Foam Cell Formation and Exploring the Biologically Active Compounds Derived From Natural Resources.Advances in pharmacological and pharmaceutical sciences · 2026Review
- Article
- Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes.Life (Basel, Switzerland) · 2025Article
- Refined Phylogenetic Ortholog Inference Reveals Coevolutionary Expansion of the MAPK Signaling Network Through Finetuning of Pathway Specificity.Journal of molecular evolution · 2025Article
- Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens.Biochemistry and biophysics reports · 2025Article
- Diffusion-based generation of gene regulatory networks from scRNA-seq data with DigNet.Genome research · 2025Article
- Thiostrepton: multifaceted biological activities and its applications in treatment of inflammatory diseases.Inflammopharmacology · 2025Review
- TPL2 kinase activity is required forFrontiers in immunology · 2025Article
- TPL2 Promotes Gastric Cancer Progression and Chemoresistance Through a Hypoxia-Induced Positive Feedback Loop with PPARδ.International journal of biological sciences · 2025Article
- MAP3K8 is a potential therapeutic target in airway epithelial inflammation.Journal of inflammation (London, England) · 2024Article
- Selective regulation of a defined subset of inflammatory and immunoregulatory genes by an NF-κB p50-IκBζ pathway.Genes & development · 2024Article
- RelA and mitogen-activated protein kinase kinase kinases potently enhance lentiviral vector production.Biochemistry and biophysics reports · 2024Article
- Interplay of Chemokines Receptors, Toll-like Receptors, and Host Immunological Pathways.Biomedicines · 2023Review
- MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell-intrinsic Amplification of Type I IFN Signaling.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors.
Funding
Abstract
The IκB kinase (IKK) complex plays a well-documented role in innate and adaptive immunity. This function has been widely attributed to its role as the central activator of the NF-κB family of transcription factors. However, another important consequence of IKK activation is the regulation of TPL-2, a MEK kinase that is required for activation of ERK-1/2 MAP kinases in myeloid cells following Toll-like receptor and TNF receptor stimulation. In unstimulated cells, TPL-2 is stoichiometrically complexed with the NF-κB inhibitory protein NF-κB1 p105, which blocks TPL-2 access to its substrate MEK, and the ubiquitin-binding protein ABIN-2 (A20-binding inhibitor of NF-κB 2), both of which are required to maintain TPL-2 protein stability. Following agonist stimulation, the IKK complex phosphorylates p105, triggering its K48-linked ubiquitination and degradation by the proteasome. This releases TPL-2 from p105-mediated inhibition, facilitating activation of MEK, in addition to modulating NF-κB activation by liberating associated Rel subunits for translocation into the nucleus. IKK-induced proteolysis of p105, therefore, can directly regulate both NF-κB and ERK MAP kinase activation via NF-κB1 p105. TPL-2 is critical for production of the proinflammatory cytokine TNF during inflammatory responses. Consequently, there has been considerable interest in the pharmaceutical industry to develop selective TPL-2 inhibitors as drugs for the treatment of TNF-dependent inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. This review summarizes our current understanding of the regulation of TPL-2 signaling function, and also the complex positive and negative roles of TPL-2 in immune and inflammatory responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.