Evidence map›Paper›PMID 20426839›Full record

ArticleMolecular cancer2010

Myc interacts with Max and Miz1 to repress C/EBPdelta promoter activity and gene expression.

Junling Si, Xueyan Yu, Yingjie Zhang, James W DeWille

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

31 citing papers in PubMed, 52 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Junling SiDepartment of Veterinary Biosciences, Ohio State University College of Veterinary Medicine, Columbus, Ohio 43210, USA.
Xueyan Yu
Yingjie Zhang
James W DeWille
The Ohio State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
C/EBP DELTA CONTROLS MAMMARY EPITH CELL G GROWTH ARRESTR01CA057607 · NCI · OHIO STATE UNIVERSITY · PI DEWILLE, JAMES W · 1999 to 2007
$2.2M
C/EBP ISOFORM EXPRESSION IN MAMMARY GLAND AND TUMORSR29CA057607 · NCI · OHIO STATE UNIVERSITY · PI DEWILLE, JAMES W · 1994 to 1999
–
NCI NIH HHS CA57607NCI NIH HHS P30 CA16058
6 · The paper itself

Abstract

background"Loss of function" alterations in CCAAT/Enhancer Binding Proteindelta (C/EBPdelta) have been reported in a number of human cancers including breast, prostate and cervical cancer, hepatocellular carcinoma and acute myeloid leukemia. C/EBPdelta gene transcription is induced during cellular quiescence and repressed during active cell cycle progression. C/EBPdelta exhibits tumor suppressor gene properties including reduced expression in cancer cell lines and tumors and promoter methylation silencing. We previously reported that C/EBPdelta expression is inversely correlated with c-Myc (Myc) expression. Aberrant Myc expression is common in cancer and transcriptional repression is a major mechanism of Myc oncogenesis. A number of tumor suppressor genes are targets of Myc transcriptional repression including C/EBPalpha, p15INK4, p21CIP1, p27KIP1 and p57KIP2. This study investigated the mechanisms underlying Myc repression of C/EBPdelta expression.

resultsMyc represses C/EBPdelta promoter activity in nontransformed mammary epithelial cells in a dose-dependent manner that requires Myc Box II, Basic Region and HLH/LZ domains. Chromatin Immunoprecipitation (ChIP) assays demonstrate that Myc, Miz1 and Max are associated with the C/EBPdelta promoter in proliferating cells, when C/EBPdelta expression is repressed. EMSAs demonstrate that Miz1 binds to a 30 bp region (-100 to -70) of the C/EBPdelta promoter which contains a putative transcription initiator (Inr) element. Miz1 functions exclusively as a repressor of C/EBPdelta promoter activity. Miz1 siRNA expression or expression of a Miz1 binding deficient Myc (MycV394D) construct reduces Myc repression of C/EBPdelta promoter activity. Max siRNA expression, or expression of a Myc construct lacking the HLH/LZ (Max interacting) region, also reduces Myc repression of C/EBPdelta promoter activity. Miz1 and Max siRNA treatments attenuate Myc repression of endogenous C/EBPdelta expression. Myc Box II interacting proteins RuvBl1 (Pontin, TIP49) and RuvBl2 (Reptin, TIP48) enhances Myc repression of C/EBPdelta promoter activity.

conclusionMyc represses C/EBPdelta expression by associating with the C/EBPdelta proximal promoter as a transient component of a repressive complex that includes Max and Miz1. RuvBl1 and RuvBl2 enhance Myc repression of C/EBPdelta promoter activity. These results identify protein interactions that mediate Myc repression of C/EBPdelta, and possibly other tumor suppressor genes, and suggest new therapeutic targets to block Myc transcriptional repression and oncogenic function.

Indexed as

AnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBlotting, WesternCCAAT-Enhancer-Binding Protein-deltaChromatin ImmunoprecipitationElectrophoretic Mobility Shift AssayEpithelial CellsFemaleGene ExpressionGene Expression RegulationImmunoprecipitationKruppel-Like Transcription FactorsMammary Glands, AnimalMicePromoter Regions, GeneticProto-Oncogene Proteins c-mycBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCCAAT-Enhancer-Binding Protein-deltaKruppel-Like Transcription FactorsMNT protein, humanMYC protein, humanProto-Oncogene Proteins c-mycRepressor ProteinsRNA, Small InterferingZBTB17 protein, human

Identifiers

PMID20426839
PMCPMC2879254
OpenAlexW2126150981

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.