ArticleThe Journal of biological chemistry2010
Apoptotic regulation by MCL-1 through heterodimerization.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- The BH3-only protein NOXA is essential for apoptosis induction by BH3-mimetics targeting BCL2 or BCL-XBritish journal of haematology · 2026Article
- Screening of the Prodiginine Molecules as BH3-mimetics against the Developed Bcl-2 Antiapoptotic Chemotherapeutic Resistance: A Molecular Docking and ADMET Study Supported by Molecular Dynamics Simulations.Current computer-aided drug design · 2026Article
- Structural basis of BAK sequestration by MCL-1 in apoptosis.Molecular cell · 2025Article
- Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1.Molecular cell · 2024Article
- Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.Cancer cell international · 2024Review
- Article
- Innate Conformational Dynamics Drive Binding Specificity in Anti-Apoptotic Proteins Mcl-1 and Bcl-2.Biochemistry · 2023Article
- Marine Polyether Phycotoxin Palytoxin Induces Apoptotic Cell Death via Mcl-1 and Bcl-2 Downregulation.Marine drugs · 2023Article
- Structural Insight into KsBcl-2 Mediated Apoptosis Inhibition by Kaposi Sarcoma Associated Herpes Virus.Viruses · 2022Article
- Structural insights into apoptotic regulation of human Bfk as a novel Bcl-2 family member.Computational and structural biotechnology journal · 2022Article
- Guanylate-binding proteins induce apoptosis of leukemia cells by regulating MCL-1 and BAK.Oncogenesis · 2021Article
- Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting.Science advances · 2021Article
- Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2.eLife · 2019Article
- Rapid Mapping of Protein Interactions Using Tag-Transfer Photocrosslinkers.Angewandte Chemie (International ed. in English) · 2018Article
- BCL-2 family proteins: changing partners in the dance towards death.Cell death and differentiation · 2018Review
- Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor.Nature cell biology · 2017Article
- Structural Insight into African Swine Fever Virus A179L-Mediated Inhibition of Apoptosis.Journal of virology · 2017Article
- The deadly landscape of pro-apoptotic BCL-2 proteins in the outer mitochondrial membrane.The FEBS journal · 2016Review
- Locating Herpesvirus Bcl-2 Homologs in the Specificity Landscape of Anti-Apoptotic Bcl-2 Proteins.Journal of molecular biology · 2015Article
- Design, synthesis and evaluation of marinopyrrole derivatives as selective inhibitors of Mcl-1 binding to pro-apoptotic Bim and dual Mcl-1/Bcl-xL inhibitors.European journal of medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Myeloid cell leukemia 1 (MCL-1), an anti-apoptotic BCL-2 family member active in the preservation of mitochondrial integrity during apoptosis, has fundamental roles in development and hematopoiesis and is dysregulated in human cancers. It bears a unique, intrinsically unstructured, N-terminal sequence, which leads to its instability in cells and hinders protein production and structural characterization. Here, we present collective data from NMR spectroscopy and titration calorimetry to reveal the selectivity of MCL-1 in binding BCL-2 homology 3 (BH3) ligands of interest for mammalian biology. The N-terminal sequence weakens the BH3 interactions but does not affect selectivity. Its removal by calpain-mediated limited proteolysis results in a stable BCL-2-like core domain of MCL-1 (cMCL-1). This core is necessary and sufficient for BH3 ligand binding. Significantly, we also characterized the in vitro protein-protein interaction between cMCL-1 and activated BID by size exclusion chromatography and NMR titrations. This interaction occurs in a very slow manner in solution but is otherwise similar to the interaction between cMCL-1 and BID-BH3 peptides. We also present the solution structure of complex cMCL-1xhBID-BH3, which completes the family portrait of MCL-1 complexes and may facilitate drug discovery against human tumors.
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Registered trials
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