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Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo

Authors: Baëza, Manon; Viala, Séverine; Heim, Marjorie; Dard, Amélie; Hudry, Bruno; Duffraisse, Marilyne; Rogulja-Ortmann, Ana; +2 Authors

Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo

Abstract

Hox proteins are well-established developmental regulators that coordinate cell fate and morphogenesis throughout embryogenesis. In contrast, our knowledge of their specific molecular modes of action is limited to the interaction with few cofactors. Here, we show that Hox proteins are able to interact with a wide range of transcription factors in the live Drosophila embryo. In this context, specificity relies on a versatile usage of conserved short linear motifs (SLiMs), which, surprisingly, often restrains the interaction potential of Hox proteins. This novel buffering activity of SLiMs was observed in different tissues and found in Hox proteins from cnidarian to mouse species. Although these interactions remain to be analysed in the context of endogenous Hox regulatory activities, our observations challenge the traditional role assigned to SLiMs and provide an alternative concept to explain how Hox interactome specificity could be achieved during the embryonic development.

Country
France
Keywords

Embryo, Nonmammalian, [SDV]Life Sciences [q-bio], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Amino Acid Motifs, 590, interactome, Mice, TARGET GENE, Drosophila Proteins, CELL REGULATION, Protein Interaction Maps, Biology (General), transcription factor, Q, R, INTERACTION MODULES, REGIONS, Hox, [SDV] Life Sciences [q-bio], TRANSCRIPTION FACTORS, Drosophila melanogaster, Genomics and Evolutionary Biology, Organ Specificity, Medicine, Oligopeptides, Protein Binding, 570, QH301-705.5, Science, embryo, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Binding, Competitive, Fluorescence, Evolution, Molecular, Structure-Activity Relationship, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, BiFC, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, development, ABDOMINAL-A, Homeodomain Proteins, BIMOLECULAR FLUORESCENCE COMPLEMENTATION, REPRESSION, DNA, PROTEIN INTERACTIONS, Intrinsically Disordered Proteins, DROSOPHILA-MELANOGASTER, Mutation, Transcription Factors

  • BIP!
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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    46
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
46
Top 10%
Top 10%
Top 10%
Green
gold