Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole

Tamas Zeke, Nicholas Morrice, Cristina Vazquez-Martin, Tricia Cohen

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    Ppp5 (protein phosphatase 5) is a serine/threonine protein phosphatase that has been conserved throughout eukaryotic evolution. In mammalian cells, FLAG-tagged Ppp5 and endogenous Ppp5 are found to interact with endogenous Hsp (heat-shock protein) 70, as well as Hsp90. Incubation of cells with arachidonic acid or the microtubule-depolymerizing agent, nocodazole, causes loss of interaction of Hsp70 and Hsp90 with FLAG-tagged Ppp5 and increase of Ppp5 activity. In response to the same treatments, endogenous Ppp5 undergoes proteolytic cleavage of the N- and C-termini, with the subsequent appearance of high-molecular-mass species. The results indicate that Ppp5 is activated by proteolysis on dissociation from Hsps, and is destroyed via the proteasome after ubiquitination. Cleavage at the C-terminus removes a nuclear localization sequence, allowing these active cleaved forms of Ppp5 to translocate to the cytoplasm. The response of Ppp5 to arachidonic acid and nocodazole suggests that Ppp5 may be required for stress-related processes that can sometimes cause cell-cycle arrest, and leads to the first description for in vivo regulation of Ppp5 activity.
    Original languageEnglish
    Pages (from-to)45-56
    Number of pages12
    JournalBiochemical Journal
    Volume385
    Issue number1
    DOIs
    Publication statusPublished - Jan 2005

    Fingerprint

    Nocodazole
    Heat-Shock Proteins
    Arachidonic Acid
    Microtubules
    Pharmaceutical Preparations
    Cells
    protein phosphatase 5
    Proteolysis
    HSP70 Heat-Shock Proteins
    Phosphoprotein Phosphatases
    Ubiquitination
    Molecular mass
    Proteasome Endopeptidase Complex
    Cell Cycle Checkpoints
    Cytoplasm

    Keywords

    • Cellular stress
    • Heat-shock protein 70 (Hsp70)
    • Heat-shock protein 90 (Hsp90)
    • Nocodazole
    • Protein serine/threonine phosphatase 5 (Ppp5/PP5)

    Cite this

    @article{2978ea063ed34a268909ae7e0f0ef596,
    title = "Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole",
    abstract = "Ppp5 (protein phosphatase 5) is a serine/threonine protein phosphatase that has been conserved throughout eukaryotic evolution. In mammalian cells, FLAG-tagged Ppp5 and endogenous Ppp5 are found to interact with endogenous Hsp (heat-shock protein) 70, as well as Hsp90. Incubation of cells with arachidonic acid or the microtubule-depolymerizing agent, nocodazole, causes loss of interaction of Hsp70 and Hsp90 with FLAG-tagged Ppp5 and increase of Ppp5 activity. In response to the same treatments, endogenous Ppp5 undergoes proteolytic cleavage of the N- and C-termini, with the subsequent appearance of high-molecular-mass species. The results indicate that Ppp5 is activated by proteolysis on dissociation from Hsps, and is destroyed via the proteasome after ubiquitination. Cleavage at the C-terminus removes a nuclear localization sequence, allowing these active cleaved forms of Ppp5 to translocate to the cytoplasm. The response of Ppp5 to arachidonic acid and nocodazole suggests that Ppp5 may be required for stress-related processes that can sometimes cause cell-cycle arrest, and leads to the first description for in vivo regulation of Ppp5 activity.",
    keywords = "Cellular stress, Heat-shock protein 70 (Hsp70), Heat-shock protein 90 (Hsp90), Nocodazole, Protein serine/threonine phosphatase 5 (Ppp5/PP5)",
    author = "Tamas Zeke and Nicholas Morrice and Cristina Vazquez-Martin and Tricia Cohen",
    note = "dc.publisher: Portland Press dc.description.sponsorship: Medical Research Council, U.K.",
    year = "2005",
    month = "1",
    doi = "10.1042/BJ20040690",
    language = "English",
    volume = "385",
    pages = "45--56",
    journal = "Biochemical Journal",
    issn = "0264-6021",
    publisher = "Portland Press",
    number = "1",

    }

    Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole. / Zeke, Tamas; Morrice, Nicholas; Vazquez-Martin, Cristina; Cohen, Tricia.

    In: Biochemical Journal, Vol. 385, No. 1, 01.2005, p. 45-56.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole

    AU - Zeke, Tamas

    AU - Morrice, Nicholas

    AU - Vazquez-Martin, Cristina

    AU - Cohen, Tricia

    N1 - dc.publisher: Portland Press dc.description.sponsorship: Medical Research Council, U.K.

    PY - 2005/1

    Y1 - 2005/1

    N2 - Ppp5 (protein phosphatase 5) is a serine/threonine protein phosphatase that has been conserved throughout eukaryotic evolution. In mammalian cells, FLAG-tagged Ppp5 and endogenous Ppp5 are found to interact with endogenous Hsp (heat-shock protein) 70, as well as Hsp90. Incubation of cells with arachidonic acid or the microtubule-depolymerizing agent, nocodazole, causes loss of interaction of Hsp70 and Hsp90 with FLAG-tagged Ppp5 and increase of Ppp5 activity. In response to the same treatments, endogenous Ppp5 undergoes proteolytic cleavage of the N- and C-termini, with the subsequent appearance of high-molecular-mass species. The results indicate that Ppp5 is activated by proteolysis on dissociation from Hsps, and is destroyed via the proteasome after ubiquitination. Cleavage at the C-terminus removes a nuclear localization sequence, allowing these active cleaved forms of Ppp5 to translocate to the cytoplasm. The response of Ppp5 to arachidonic acid and nocodazole suggests that Ppp5 may be required for stress-related processes that can sometimes cause cell-cycle arrest, and leads to the first description for in vivo regulation of Ppp5 activity.

    AB - Ppp5 (protein phosphatase 5) is a serine/threonine protein phosphatase that has been conserved throughout eukaryotic evolution. In mammalian cells, FLAG-tagged Ppp5 and endogenous Ppp5 are found to interact with endogenous Hsp (heat-shock protein) 70, as well as Hsp90. Incubation of cells with arachidonic acid or the microtubule-depolymerizing agent, nocodazole, causes loss of interaction of Hsp70 and Hsp90 with FLAG-tagged Ppp5 and increase of Ppp5 activity. In response to the same treatments, endogenous Ppp5 undergoes proteolytic cleavage of the N- and C-termini, with the subsequent appearance of high-molecular-mass species. The results indicate that Ppp5 is activated by proteolysis on dissociation from Hsps, and is destroyed via the proteasome after ubiquitination. Cleavage at the C-terminus removes a nuclear localization sequence, allowing these active cleaved forms of Ppp5 to translocate to the cytoplasm. The response of Ppp5 to arachidonic acid and nocodazole suggests that Ppp5 may be required for stress-related processes that can sometimes cause cell-cycle arrest, and leads to the first description for in vivo regulation of Ppp5 activity.

    KW - Cellular stress

    KW - Heat-shock protein 70 (Hsp70)

    KW - Heat-shock protein 90 (Hsp90)

    KW - Nocodazole

    KW - Protein serine/threonine phosphatase 5 (Ppp5/PP5)

    U2 - 10.1042/BJ20040690

    DO - 10.1042/BJ20040690

    M3 - Article

    VL - 385

    SP - 45

    EP - 56

    JO - Biochemical Journal

    JF - Biochemical Journal

    SN - 0264-6021

    IS - 1

    ER -