Evidence map›Paper›PMID 20392693›Full record

ArticleThe Journal of biological chemistry2010

Apoptotic regulation by MCL-1 through heterodimerization.

Qian Liu, Tudor Moldoveanu, Tara Sprules, Edna Matta-Camacho, Nura Mansur-Azzam, Kalle Gehring

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed.

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  14. Rapid Mapping of Protein Interactions Using Tag-Transfer Photocrosslinkers.Angewandte Chemie (International ed. in English) · 2018
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Qian LiuDepartment of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Tudor Moldoveanu
Tara Sprules
Edna Matta-Camacho
Nura Mansur-Azzam
Kalle Gehring

Funding

Canadian Institutes of Health Research MOP-81277
6 · The paper itself

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.

Indexed as

ApoptosisAmino Acid SequenceCalorimetryCalpainDimerizationGene Expression Regulation, NeoplasticHumansLigandsMagnetic Resonance SpectroscopyMitochondriaMolecular Sequence DataMyeloid Cell Leukemia Sequence 1 ProteinProtein Interaction MappingProto-Oncogene Proteins c-bcl-2Sequence Homology, Amino AcidCalpainLigandsMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2

Identifiers

PMID20392693
PMCPMC2885240

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.