Evidence map›Paper›PMID 10022857›Full record

ArticleMolecular and cellular biology1999

C/EBPalpha regulates generation of C/EBPbeta isoforms through activation of specific proteolytic cleavage.

A L Welm, N A Timchenko, G J Darlington

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 108 citations in OpenAlex.

  1. Review
  2. The "Janus" Role of C/EBPs Family Members in Cancer Progression.International journal of molecular sciences · 2020
    Review
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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

3 authors at 1 institution in 1 country.

A L WelmDepartment of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
N A Timchenko
G J Darlington
Baylor College of Medicine · US

Funding

Molecular Mechanisms of C/EBP Alpha Mediated Growth ArrestR01GM055188 · NIGMS · CINCINNATI CHILDRENS HOSP MED CTR · PI TIMCHENKO, NIKOLAI A. · 1997 to 2013
$3.3M
C/EBP ALPHA REGULATION OF ACUTE PHASE RESPONSE IN VIVOR01DK053045 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI DARLINGTON, GRETCHEN J. · 1997 to 2004
$1.4M
Thymic Involution And Age-associated Changes In T CellsZ01AG000766 · NIA · NATIONAL INSTITUTE ON AGING · PI TAUB, DENNIS D. · 2001 to 2008
$799k
Intramural NIH HHS Z01 AG000766NIDDK NIH HHS R01 DK053045NIDDK NIH HHS R01-DK53045NIGMS NIH HHS GM55188NIGMS NIH HHS R01 GM055188
6 · The paper itself

Abstract

C/EBPalpha and C/EBPbeta are intronless genes that can produce several N-terminally truncated isoforms through the process of alternative translation initiation at downstream AUG codons. C/EBPbeta has been reported to produce four isoforms: full-length 38-kDa C/EBPbeta, 35-kDa LAP (liver-enriched transcriptional activator protein), 21-kDa LIP (liver-enriched transcriptional inhibitory protein), and a 14-kDa isoform. In this report, we investigated the mechanisms by which C/EBPbeta isoforms are generated in the liver and in cultured cells. Using an in vitro translation system, we found that LIP can be generated by two mechanisms: alternative translation and a novel mechanism-specific proteolytic cleavage of full-length C/EBPbeta. Studies of mice in which the C/EBPalpha gene had been deleted (C/EBPalpha-/-) showed that the regulation of C/EBPbeta proteolysis is dependent on C/EBPalpha. The induction of C/EBPalpha in cultured cells leads to induced cleavage of C/EBPbeta to generate the LIP isoform. We characterized the cleavage activity in mouse liver extracts and found that the proteolytic cleavage activity is specific to prenatal and newborn livers, is sensitive to chymostatin, and is completely abolished in C/EBPalpha-/- animals. The lack of cleavage activity in the livers of C/EBPalpha-/- mice correlates with the decreased levels of LIP in the livers of these animals. Analysis of LIP production during liver regeneration showed that, in this system, the transient induction of LIP is dependent on the third AUG codon and most likely involves translational control. We propose that there are two mechanisms by which C/EBPbeta isoforms might be generated in the liver and in cultured cells: one that is determined by translation and a second that involves C/EBPalpha-dependent, specific proteolytic cleavage of full-length C/EBPbeta. The latter mechanism implicates C/EBPalpha in the regulation of posttranslational generation of the dominant negative C/EBPbeta isoform, LIP.

Indexed as

AnimalsAnimals, NewbornCCAAT-Enhancer-Binding Protein-betaCCAAT-Enhancer-Binding ProteinsCell-Free SystemCell LineCysteine EndopeptidasesCysteine Proteinase InhibitorsDimerizationDNADNA-Binding ProteinsEnzyme ActivationLiverLiver RegenerationMiceMice, KnockoutCCAAT-Enhancer-Binding Protein-betaCCAAT-Enhancer-Binding ProteinschymostatinCysteine EndopeptidasesCysteine Proteinase InhibitorsDNADNA-Binding ProteinsNuclear ProteinsOligopeptidesProtein IsoformsRepressor ProteinsSerine Proteinase InhibitorsTissue Extracts

Identifiers

PMID10022857
PMCPMC83963
OpenAlexW2120954095

What OpenQuestion holds

Texttitle and abstract
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.