A new kind of membrane-tethered eukaryotic transcription factor that shares an auto-proteolytic processing mechanism with bacteriophage tail-spike proteins

Hiroshi Senoo, Tsuyoshi Araki, Masashi Fukuzawa, Jeffrey G. Williams (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    MrfA, a transcription factor that regulates Dictyostelium prestalk cell differentiation, is an orthologue of the animal Myelin-gene Regulatory Factor (MRF) proteins. We show that the MRFs contain a predicted trans-membrane domain, suggesting that they are synthesized as membrane-tethered proteins that are then proteolytically released. We confirm this for MrfA but report a radically different mode of processing from that of paradigmatic tethered transcriptional regulators; which are cleaved within the trans-membrane domain by a dedicated protease. Instead an auto-proteolytic cleavage mechanism, previously only described for the intramolecular chaperone domains of bacteriophage tail-spike proteins, processes MrfA and, by implication, the metazoan MRF proteins. We also present evidence that the auto-proteolysis of MrfA occurs rapidly and constitutively in the ER and that its specific role in prestalk cell differentiation is conferred by the regulated nuclear translocation of the liberated fragment.
    Original languageEnglish
    Article number133231
    JournalJournal of Cell Science
    Volumen/a
    Early online date17 Sep 2013
    DOIs
    Publication statusPublished - 2013

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    Regulator Genes
    Myelin Sheath
    Cell Differentiation
    Transcription Factors
    Dictyostelium
    Membranes
    Proteolysis
    Membrane Proteins
    Proteins
    Peptide Hydrolases
    bacteriophage tailspike protein

    Cite this

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    title = "A new kind of membrane-tethered eukaryotic transcription factor that shares an auto-proteolytic processing mechanism with bacteriophage tail-spike proteins",
    abstract = "MrfA, a transcription factor that regulates Dictyostelium prestalk cell differentiation, is an orthologue of the animal Myelin-gene Regulatory Factor (MRF) proteins. We show that the MRFs contain a predicted trans-membrane domain, suggesting that they are synthesized as membrane-tethered proteins that are then proteolytically released. We confirm this for MrfA but report a radically different mode of processing from that of paradigmatic tethered transcriptional regulators; which are cleaved within the trans-membrane domain by a dedicated protease. Instead an auto-proteolytic cleavage mechanism, previously only described for the intramolecular chaperone domains of bacteriophage tail-spike proteins, processes MrfA and, by implication, the metazoan MRF proteins. We also present evidence that the auto-proteolysis of MrfA occurs rapidly and constitutively in the ER and that its specific role in prestalk cell differentiation is conferred by the regulated nuclear translocation of the liberated fragment.",
    author = "Hiroshi Senoo and Tsuyoshi Araki and Masashi Fukuzawa and Williams, {Jeffrey G.}",
    year = "2013",
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    language = "English",
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    journal = "Journal of Cell Science",
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    A new kind of membrane-tethered eukaryotic transcription factor that shares an auto-proteolytic processing mechanism with bacteriophage tail-spike proteins. / Senoo, Hiroshi; Araki, Tsuyoshi; Fukuzawa, Masashi; Williams, Jeffrey G. (Lead / Corresponding author).

    In: Journal of Cell Science, Vol. n/a, 133231, 2013.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A new kind of membrane-tethered eukaryotic transcription factor that shares an auto-proteolytic processing mechanism with bacteriophage tail-spike proteins

    AU - Senoo, Hiroshi

    AU - Araki, Tsuyoshi

    AU - Fukuzawa, Masashi

    AU - Williams, Jeffrey G.

    PY - 2013

    Y1 - 2013

    N2 - MrfA, a transcription factor that regulates Dictyostelium prestalk cell differentiation, is an orthologue of the animal Myelin-gene Regulatory Factor (MRF) proteins. We show that the MRFs contain a predicted trans-membrane domain, suggesting that they are synthesized as membrane-tethered proteins that are then proteolytically released. We confirm this for MrfA but report a radically different mode of processing from that of paradigmatic tethered transcriptional regulators; which are cleaved within the trans-membrane domain by a dedicated protease. Instead an auto-proteolytic cleavage mechanism, previously only described for the intramolecular chaperone domains of bacteriophage tail-spike proteins, processes MrfA and, by implication, the metazoan MRF proteins. We also present evidence that the auto-proteolysis of MrfA occurs rapidly and constitutively in the ER and that its specific role in prestalk cell differentiation is conferred by the regulated nuclear translocation of the liberated fragment.

    AB - MrfA, a transcription factor that regulates Dictyostelium prestalk cell differentiation, is an orthologue of the animal Myelin-gene Regulatory Factor (MRF) proteins. We show that the MRFs contain a predicted trans-membrane domain, suggesting that they are synthesized as membrane-tethered proteins that are then proteolytically released. We confirm this for MrfA but report a radically different mode of processing from that of paradigmatic tethered transcriptional regulators; which are cleaved within the trans-membrane domain by a dedicated protease. Instead an auto-proteolytic cleavage mechanism, previously only described for the intramolecular chaperone domains of bacteriophage tail-spike proteins, processes MrfA and, by implication, the metazoan MRF proteins. We also present evidence that the auto-proteolysis of MrfA occurs rapidly and constitutively in the ER and that its specific role in prestalk cell differentiation is conferred by the regulated nuclear translocation of the liberated fragment.

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    DO - 10.1242/jcs.133231

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