Evidence map›Paper›PMID 16087734›Full record

ArticleNucleic acids research2005

Group 13 HOX proteins interact with the MH2 domain of R-Smads and modulate Smad transcriptional activation functions independent of HOX DNA-binding capability.

Thomas M Williams, Melissa E Williams, Joanne H Heaton, Thomas D Gelehrter, Jeffrey W Innis

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

21 citing papers in PubMed, 53 citations in OpenAlex.

  1. Toward a cell-type-specific lung HOX code.Frontiers in cell and developmental biology · 2026
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  20. Hox specificity unique roles for cofactors and collaborators.Current topics in developmental biology · 2009
    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

5 authors at 1 institution in 1 country.

Thomas M WilliamsDepartment of Human Genetics, University of Michigan Ann Arbor, MI, USA.
Melissa E Williams
Joanne H Heaton
Thomas D Gelehrter
Jeffrey W Innis
University of Michigan–Ann Arbor · US

Funding

PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
HOXA13 AMINO-TERMINAL FUNCTIONAL DOMAINSR01HD037486 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI INNIS, JEFFREY W · 2000 to 2004
$1.2M
NICHD NIH HHS R01 HD037486NICHD NIH HHS R01HD37486NIGMS NIH HHS T32 GM007544NIGMS NIH HHS T32 GM07544
6 · The paper itself

Abstract

Interactions with co-factors provide a means by which HOX proteins exert specificity. To identify candidate protein interactors of HOXA13, we created and screened an E11.5-E12.5, distal limb bud yeast two-hybrid prey library. Among the interactors, we isolated the BMP-signaling effector Smad5, which interacted with the paralogous HOXD13 but not with HOXA11 or HOXA9, revealing unique interaction capabilities of the AbdB-like HOX proteins. Using deletion mutants, we determined that the MH2 domain of Smad5 is necessary for HOXA13 interaction. This is the first report demonstrating an interaction between HOX proteins and the MH2 domain of Smad proteins. HOXA13 and HOXD13 also bind to other BMP and TGF-beta/Activin-regulated Smad proteins including Smad1 and Smad2, but not Smad4. Furthermore, HOXD13 could be co-immunoprecipitated with Smad1 from cells. Expression of HOXA13, HOXD13 or a HOXD13 homeodomain mutant (HOXD13(IQN>AAA)) antagonized TGF-beta-stimulated transcriptional activation of the pAdtrack-3TP-Lux reporter vector in Mv1Lu cells as well as the Smad3/Smad4-activated pTRS6-E1b promoter in Hep3B cells. Finally, using mammalian one-hybrid assay, we show that transcriptional activation by a GAL4/Smad3-C-terminus fusion protein is specifically inhibited by HOXA13. Our results identify a new co-factor for HOX group 13 proteins and suggest that HOX proteins may modulate Smad-mediated transcriptional activity through protein-protein interactions without the requirement for HOX monomeric DNA-binding capability.

Indexed as

Transcriptional ActivationAnimalsBone Morphogenetic ProteinsCell LineDNA-Binding ProteinsExtremitiesGene LibraryHomeodomain ProteinsHumansMiceMice, Inbred C57BLPhosphoproteinsProtein Structure, TertiarySmad1 ProteinSmad3 ProteinSmad5 ProteinBone Morphogenetic ProteinsDNA-Binding Proteinshomeobox protein HOXA13Homeodomain ProteinsHOXD13 protein, humanHoxd13 protein, mousePhosphoproteinsSmad1 ProteinSMAD1 protein, humanSmad1 protein, mouseSmad3 ProteinSMAD3 protein, humanSmad3 protein, mouseSmad5 ProteinSMAD5 protein, humanSmad5 protein, mouseSmad ProteinsTGFB1 protein, humanTgfb1 protein, mouseTrans-ActivatorsTranscription FactorsTransforming Growth Factor betaTransforming Growth Factor beta1

Identifiers

PMID16087734
PMCPMC1183491
OpenAlexW1964794638

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.