Evidence map›Paper›PMID 31189926›Full record

ArticleCell death and differentiation2020

Dynein light chain binding determines complex formation and posttranslational stability of the Bcl-2 family members Bmf and Bim.

Prafull Kumar Singh, Aristomenis Roukounakis, Arnim Weber, Kushal Kumar Das, Benedicte Sohm, Andreas Villunger, Ana J Garcia-Saez, Georg Häcker

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
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

8 authors at 4 institutions in 3 countries.

Prafull Kumar SinghInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, Medical Center - University of Freiburg, 79104, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0529-9748
Aristomenis RoukounakisInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, Medical Center - University of Freiburg, 79104, Freiburg, Germany.
Arnim WeberInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, Medical Center - University of Freiburg, 79104, Freiburg, Germany.
Kushal Kumar DasInterfaculty Institute of Biochemistry (IFIB), University of Tübingen, 72076, Tübingen, Germany.
Benedicte SohmDivision of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020, Innsbruck, Austria.
Andreas VillungerDivision of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020, Innsbruck, Austria.
Ana J Garcia-SaezInterfaculty Institute of Biochemistry (IFIB), University of Tübingen, 72076, Tübingen, Germany.ORCID http://orcid.org/0000-0002-3894-5945
Georg HäckerInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, Medical Center - University of Freiburg, 79104, Freiburg, Germany. georg.haecker@uniklinik-freiburg.de.
University of Freiburg · DEUniversity of Tübingen · DECentre National de la Recherche Scientifique · FRInnsbruck Medical University · AT

Funding

Austrian Science Fund FWF I 3271
6 · The paper itself

Abstract

The BH3-only class of Bcl-2 family proteins triggers mitochondrial apoptosis. Several mechanisms are used to restrain the pro-apoptotic activity of these proteins. Dynein light chain (DYNLL) 1 and 2 has been proposed to negatively regulate the activity of Bim and Bmf, respectively, and the Bim-DYNLL1 interaction leads to the formation of large protein complexes on mitochondria. Here we found that Bim and Bmf interact with both isoforms of DYNLL (DYNLL1 and DYNLL2). DYNLL1/2 not only induced homo-dimerization of Bim and Bmf but also led to the formation of ternary complexes (Bim-DYNLL-Bmf), both in cell-free and in cellular systems. DYNLL-induced oligomerization stabilized Bmf in cultured cells and inhibited its degradation by the ubiquitin-independent 20S proteasome in a cell-free system. Surprisingly, overexpression of wild-type Bmf but not of a DYNLL-binding-deficient mutant induced degradation of endogenous Bim in different cell lines, but both variants sensitized to apoptosis. Mutant Bmf incapable of interacting with anti-apoptotic Bcl-2 proteins and of inducing apoptosis still caused Bim degradation. These results suggest that Bmf overexpression-induced Bim degradation is not due to the displacement of Bim from anti-apoptotic Bcl-2 proteins but a direct consequence of the modulation of Bim-DYNLL association. A peptide derived from the DYNLL-binding domain of Bim also led to the degradation of Bim as well as of its preferred binding partner Mcl-1. Thus DYNLL regulates the mitochondrial pathway of apoptosis by determining the stability of Bmf, Bim, and Mcl-1 proteins.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsBcl-2-Like Protein 11Binding SitesCells, CulturedCytoplasmic DyneinsHumansMiceMice, Inbred C57BLMice, KnockoutAdaptor Proteins, Signal TransducingBcl2l11 protein, mouseBcl-2-Like Protein 11Bmf protein, mouseCytoplasmic DyneinsDYNLL1 protein, mouseDynll2 protein, mouse

Identifiers

PMID31189926
PMCPMC7206095
OpenAlexW2953233918

What OpenQuestion holds

Textmetadata
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.