A multiprotein binding interface in an intrinsically disordered region of the tumor suppressor protein interferon regulatory factor-1

Vikram Narayan, Petr Halada, Lenka Hernychová, Yuh Ping Chong, Jitka Žáková, Ted R Hupp, Borivoj Vojtesek, Kathryn L Ball (Lead / Corresponding author)

    Research output: Contribution to journalArticle

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    Abstract

    The interferon-regulated transcription factor and tumor suppressor protein IRF-1 is predicted to be largely disordered outside of the DNA-binding domain. One of the advantages of intrinsically disordered protein domains is thought to be their ability to take part in multiple, specific but low affinity protein interactions; however, relatively few IRF-1-interacting proteins have been described. The recent identification of a functional binding interface for the E3-ubiquitin ligase CHIP within the major disordered domain of IRF-1 led us to ask whether this region might be employed more widely by regulators of IRF-1 function. Here we describe the use of peptide aptamer-based affinity chromatography coupled with mass spectrometry to define a multiprotein binding interface on IRF-1 (Mf2 domain; amino acids 106-140) and to identify Mf2-binding proteins from A375 cells. Based on their function as known transcriptional regulators, a selection of the Mf2 domain-binding proteins (NPM1, TRIM28, and YB-1) have been validated using in vitro and cell-based assays. Interestingly, although NPM1, TRIM28, and YB-1 all bind to the Mf2 domain, they have differing amino acid specificities, demonstrating the degree of combinatorial diversity and specificity available through linear interaction motifs.
    Original languageEnglish
    Pages (from-to)14291-14303
    Number of pages13
    JournalJournal of Biological Chemistry
    Volume286
    Issue number16
    DOIs
    Publication statusPublished - 22 Apr 2011

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    Interferon Regulatory Factor-1
    Tumor Suppressor Proteins
    Peptide Aptamers
    Carrier Proteins
    Intrinsically Disordered Proteins
    Affinity chromatography
    Amino Acids
    Ubiquitin-Protein Ligases
    Affinity Chromatography
    Interferons
    Mass spectrometry
    Assays
    Mass Spectrometry
    Proteins
    Transcription Factors
    DNA

    Cite this

    Narayan, Vikram ; Halada, Petr ; Hernychová, Lenka ; Chong, Yuh Ping ; Žáková, Jitka ; Hupp, Ted R ; Vojtesek, Borivoj ; Ball, Kathryn L. / A multiprotein binding interface in an intrinsically disordered region of the tumor suppressor protein interferon regulatory factor-1. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 16. pp. 14291-14303.
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    abstract = "The interferon-regulated transcription factor and tumor suppressor protein IRF-1 is predicted to be largely disordered outside of the DNA-binding domain. One of the advantages of intrinsically disordered protein domains is thought to be their ability to take part in multiple, specific but low affinity protein interactions; however, relatively few IRF-1-interacting proteins have been described. The recent identification of a functional binding interface for the E3-ubiquitin ligase CHIP within the major disordered domain of IRF-1 led us to ask whether this region might be employed more widely by regulators of IRF-1 function. Here we describe the use of peptide aptamer-based affinity chromatography coupled with mass spectrometry to define a multiprotein binding interface on IRF-1 (Mf2 domain; amino acids 106-140) and to identify Mf2-binding proteins from A375 cells. Based on their function as known transcriptional regulators, a selection of the Mf2 domain-binding proteins (NPM1, TRIM28, and YB-1) have been validated using in vitro and cell-based assays. Interestingly, although NPM1, TRIM28, and YB-1 all bind to the Mf2 domain, they have differing amino acid specificities, demonstrating the degree of combinatorial diversity and specificity available through linear interaction motifs.",
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    Narayan, V, Halada, P, Hernychová, L, Chong, YP, Žáková, J, Hupp, TR, Vojtesek, B & Ball, KL 2011, 'A multiprotein binding interface in an intrinsically disordered region of the tumor suppressor protein interferon regulatory factor-1', Journal of Biological Chemistry, vol. 286, no. 16, pp. 14291-14303. https://doi.org/10.1074/jbc.M110.204602

    A multiprotein binding interface in an intrinsically disordered region of the tumor suppressor protein interferon regulatory factor-1. / Narayan, Vikram; Halada, Petr; Hernychová, Lenka; Chong, Yuh Ping; Žáková, Jitka; Hupp, Ted R; Vojtesek, Borivoj; Ball, Kathryn L (Lead / Corresponding author).

    In: Journal of Biological Chemistry, Vol. 286, No. 16, 22.04.2011, p. 14291-14303.

    Research output: Contribution to journalArticle

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    T1 - A multiprotein binding interface in an intrinsically disordered region of the tumor suppressor protein interferon regulatory factor-1

    AU - Narayan, Vikram

    AU - Halada, Petr

    AU - Hernychová, Lenka

    AU - Chong, Yuh Ping

    AU - Žáková, Jitka

    AU - Hupp, Ted R

    AU - Vojtesek, Borivoj

    AU - Ball, Kathryn L

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