ArticleInternational journal of biological macromolecules2018
Probing the interaction interface of the GADD45β/MKK7 and MKK7/DTP3 complexes by chemical cross-linking mass spectrometry.
Article in International journal of biological macromolecules, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting the JNK Gatekeepers: Structural Evolution and Medicinal Chemistry of MKK4 and MKK7 Inhibitors.Molecules (Basel, Switzerland) · 2026Review
- Selection of short Gadd45β-binding peptides through a synergistic computational and biophysical approach.Protein science : a publication of the Protein Society · 2025Article
- Identification and Experimental Validation of PANoptosis-Related Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics Analysis.Journal of inflammation research · 2025Article
- NF-κB: Governing Macrophages in Cancer.Genes · 2024Review
- Targeting Protein-Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches.International journal of molecular sciences · 2023Review
- Gadd45 in Normal Hematopoiesis and Leukemia.Advances in experimental medicine and biology · 2022Article
- Gadd45 Proteins in Immunity 2.0.Advances in experimental medicine and biology · 2022Article
- Mitogen-activated protein kinase kinase 7 in inflammatory, cancer, and neurological diseases.Frontiers in cell and developmental biology · 2022Review
- Members of the GADD45 Protein Family Show Distinct Propensities to form Toxic Amyloid-Like Aggregates in Physiological Conditions.International journal of molecular sciences · 2021Article
- The Screening of Combinatorial Peptide Libraries for Targeting Key Molecules or Protein-Protein Interactions in the NF-κB Pathway.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Insights into the Interaction Mechanism of DTP3 with MKK7 by Using STD-NMR and Computational Approaches.Biomedicines · 2020Article
- Non-'classical' MEKs: A review of MEK3-7 inhibitors.Bioorganic & medicinal chemistry letters · 2020Review
- Cancer gene therapy by NF-κB-activated cancer cell-specific expression of CRISPR/Cas9 targeting telomeres.Gene therapy · 2020Article
- Mathematical modelling of the role of GADD45β in the pathogenesis of multiple myeloma.Royal Society open science · 2020Article
- GADD45B Promotes Glucose-Induced Renal Tubular Epithelial-Mesenchymal Transition and ApoptosisFrontiers in physiology · 2020Article
- Preclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7 inhibitor and clinical candidate, DTP3.Toxicology reports · 2019Article
- MKK7, the essential regulator of JNK signaling involved in cancer cell survival: a newly emerging anticancer therapeutic target.Therapeutic advances in medical oncology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
GADD45β is selectively and constitutively expressed in Multiple Myeloma cells, and this expression correlates with an unfavourable clinical outcome. GADD45β physically interacts with the JNK kinase, MKK7, inhibiting its activity to enable the survival of cancer cells. DTP3 is a small peptide inhibitor of the GADD45β/MKK7 complex and is able to restore MKK7/JNK activation, thereby promoting selective cell death of GADD45β-overexpressing cancer cells. Enzymatic MS foot-printing and diazirine-based chemical cross-linking MS (CX-MS) strategies were applied to study the interactions between GADD45β and MKK7 kinase domain (MKK7_KD) and between DTP3 and MKK7_KD. Our data show that the binding between GADD45β and MKK7 largely occurs between GADD45β loop 2 (region 103-117) and the kinase enzymatic pocket. We also show that DTP3 interferes with this GADD45β/MKK7 interaction by contacting the MKK7 peptides, 113-136 and 259-274. Accordingly, an MKK7_KD Δ(101-136) variant lacking Trp135 did not produce a fluorescence quenching effect upon the binding of DTP3. The assessment of the interaction between GADD45β and MKK7 and the elucidation of the recognition surfaces between DTP3 and MKK7 significantly advance the understanding of the mechanism underlying the inhibition of the GADD45β/MKK7 interaction by DTP3 and pave the way to the design of small-molecule DTP3 analogues.
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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.