PMID: identifiant
de la référence Pubmed : |
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 (22046139)  |
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| titre : |
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Insights into Hox protein function from a large scale combinatorial analysis of protein domains. |
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| auteur(s) : |
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Samir Merabet1, Isma Litim-Mecheri1, Daniel Karlsson2, Richa Dixit3, Mehdi Saadaoui1, Bruno Monier1, Christine Brun1, 4, Stefan Thor2, K. Vijayraghavan3, Laurent Perrin1, Jacques Pradel1, Yacine Graba ( ) 1 |
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| laboratoire : |
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| résumé : |
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Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences. |
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| domaine : |
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Sciences du Vivant/Génétique
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1553-7390 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1371/journal.pgen.1002302 |
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| journal : |
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| Audience : |
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internationale |
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| date de publication : |
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10/2011 |
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date de publication
électronique : |
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27/10/2011 |
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| volume : |
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7 |
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| numéro : |
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10 |
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| page, identifiant, ... : |
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e1002302 |
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| Descripteur(s) MeSH : |
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Animals – Body Patterning – Cell Lineage – Central Nervous System – DNA-Binding Proteins – Drosophila Proteins – Drosophila melanogaster – Gene Expression Regulation – Developmental – Genetic Association Studies – Mutation – Nuclear Proteins – Protein Structure – Tertiary – Transcription Factors – Wnt1 Protein |
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| contrat, financement : |
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Work in the YG and JP laboratory is supported by the CNRS, Université de la Méditerranée, and grants from ANR, FRM, CEFIPRA, and ARC; work in the ST laboratory is supported by the Swedish Research Council, the Swedish Strategic Research Foundation, the Knut and Alice Wallenberg Foundation, the Swedish "Hjärnfonden," "Cancerfonden," and the Swedish Royal Academy of Sciences; work in the LP laboratory is supported by the CNRS, Université de la Méditerrannée, and grants from ANR and AFM. |
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