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

    28 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

    Keywords

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

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