Evidence map›Paper›PMID 39367171›Full record

ArticleLeukemia2024

Rapid increase of C/EBPα p42 induces growth arrest of acute myeloid leukemia (AML) cells by Cop1 deletion in Trib1-expressing AML.

Yoshitaka Sunami, Seiko Yoshino, Yukari Yamazaki, Takashi Iwamoto, Takuro Nakamura

Abstract read
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In one paragraph

Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. RNA activation ofMolecular therapy. Nucleic acids · 2025
    Article
  3. Article
  4. Article
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

5 authors.

Yoshitaka SunamiDepartment of Experimental Pathology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Seiko YoshinoDepartment of Molecular Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0009-0003-0099-0550
Yukari YamazakiDepartment of Experimental Pathology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Takashi IwamotoDepartment of Experimental Pathology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Takuro NakamuraDepartment of Experimental Pathology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan. takuron@tokyo-med.ac.jp.ORCID 0000-0002-0419-7547

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) 19H01035MEXT | Japan Society for the Promotion of Science (JSPS) 22K08492
6 · The paper itself

Abstract

Cop1 encodes a ubiquitin E3 ligase that has been well preserved during evolution in both plants and metazoans. In metazoans, the C/EBP family transcription factors are targets for degradation by Cop1, and this process is regulated by the Tribbles pseudokinase family. Over-expression of Tribbles homolog 1 (Trib1) induces acute myeloid leukemia (AML) via Cop1-dependent degradation of the C/EBPα p42 isoform. Here, we induced rapid growth arrest and granulocytic differentiation of Trib1-expressing AML cells using a Cop1 conditional knockout (KO), which is associated with a transient increase in the C/EBPα p42 isoform. The growth-suppressive effect of Cop1 KO was canceled by silencing of Cebpa and reinforced by exogenous expression of the p42 isoform. Moreover, Cop1 KO improved the survival of recipients transplanted with Trib1-expressing AML cells. We further identified a marked increase in Trib1 protein expression in Cop1 KO, indicating that Trib1 is self-degraded by the Cop1 degradosome. COP1 downregulation also inhibits the proliferation of human AML cells in a TRIB1-dependent manner. Taken together, our results provide new insights into the role of Trib1/Cop1 machinery in the C/EBPα p42-dependent leukemogenic activity, and a novel idea to develop new therapeutics.

Indexed as

Intracellular Signaling Peptides and ProteinsLeukemia, Myeloid, AcuteProtein Serine-Threonine KinasesUbiquitin-Protein LigasesAnimalsCCAAT-Enhancer-Binding Protein-alphaCCAAT-Enhancer-Binding ProteinsCell DifferentiationCell ProliferationHumansMiceMice, KnockoutNuclear ProteinsProtein IsoformsCCAAT-Enhancer-Binding Protein-alphaCCAAT-Enhancer-Binding ProteinsCOP1 protein, humanCOP1 protein, mouseIntracellular Signaling Peptides and ProteinsNuclear ProteinsProtein IsoformsProtein Serine-Threonine KinasesTRIB1 protein, humanTrib1 protein, mouseUbiquitin-Protein Ligases

Identifiers

PMID39367171

What OpenQuestion holds

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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.