Evidence map›Paper›PMID 10594012›Full record

ArticleMolecular and cellular biology2000

Auto-inhibition and partner proteins, core-binding factor beta (CBFbeta) and Ets-1, modulate DNA binding by CBFalpha2 (AML1).

T L Gu, T L Goetz, B J Graves, N A Speck

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

80 citing papers in PubMed, 149 citations in OpenAlex.

  1. Article
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20 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

T L GuDepartment of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
T L Goetz
B J Graves
N A Speck
Dartmouth College · USUniversity of Utah · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
Transcriptional Control Mechanisms by ETS FactorsR01GM038663 · NIGMS · UNIVERSITY OF UTAH · PI GRAVES, BARBARA J · 1992 to 2015
$3.9M
BIOCHEMISTRY OF LEUKEMIA VIRUS CORE-BINDING FACTORR01CA058343 · NCI · DARTMOUTH COLLEGE · PI SPECK, NANCY ASMUSSEN · 1993 to 2007
$3.0M
Tyloindicines: Chemistry and BiologyR01CA090602 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI GEORG, GUNDA I. · 2002 to 2006
$1.6M
Structure/Function of CBFbetaR01CA075611 · NCI · DARTMOUTH COLLEGE · PI SPECK, NANCY ASMUSSEN · 1997 to 2006
$1.6M
NCI NIH HHS CA75611NCI NIH HHS P30 CA042014NCI NIH HHS R01 CA058343NCI NIH HHS R01 CA075611NCI NIH HHS R01 CA090602NCI NIH HHS R01 CA58343NIGMS NIH HHS R01 GM038663NIGMS NIH HHS R01 GM38663
6 · The paper itself

Abstract

Core-binding factor alpha2 (CBFalpha2; otherwise known as AML1 or PEBP2alphaB) is a DNA-binding subunit in the family of core-binding factors (CBFs), heterodimeric transcription factors that play pivotal roles in multiple developmental processes in mammals, including hematopoiesis and bone development. The Runt domain in CBFalpha2 (amino acids 51 to 178) mediates DNA binding and heterodimerization with the non-DNA-binding CBFbeta subunit. Both the CBFbeta subunit and the DNA-binding protein Ets-1 stimulate DNA binding by the CBFalpha2 protein. Here we quantify and compare the extent of cooperativity between CBFalpha2, CBFbeta, and Ets-1. We also identify auto-inhibitory sequences within CBFalpha2 and sequences that modulate its interactions with CBFbeta and Ets-1. We show that sequences in the CBFalpha2 Runt domain and sequences C terminal to amino acid 214 inhibit DNA binding. Sequences C terminal to amino acid 214 also inhibit heterodimerization with the non-DNA-binding CBFbeta subunit, particularly heterodimerization off DNA. CBFbeta rescinds the intramolecular inhibition of CBFalpha2, stimulating DNA binding approximately 40-fold. In comparison, Ets-1 stimulates CBFalpha2 DNA binding 7- to 10-fold. Although the Runt domain alone is sufficient for heterodimerization with CBFbeta, sequences N terminal to amino acid 41 and between amino acids 190 and 214 are required for cooperative DNA binding with Ets-1. Cooperative DNA binding with Ets-1 is less pronounced with the CBFalpha2-CBFbeta heterodimer than with CBFalpha2 alone. These analyses demonstrate that CBFalpha2 is subject to both negative regulation by intramolecular interactions, and positive regulation by two alternative partnerships.

Indexed as

AnimalsBinding SitesCore Binding Factor Alpha 2 SubunitDNADNA-Binding ProteinsNucleic Acid ConformationProtein BindingProtein ConformationProto-Oncogene Protein c-ets-1Proto-Oncogene ProteinsProto-Oncogene Proteins c-etsTranscription Factor AP-2Transcription FactorsCore Binding Factor Alpha 2 SubunitDNADNA-Binding ProteinsProto-Oncogene Protein c-ets-1Proto-Oncogene ProteinsProto-Oncogene Proteins c-etsTranscription Factor AP-2Transcription Factors

Identifiers

PMID10594012
PMCPMC85059
OpenAlexW2124515729

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.