5hpe: Difference between revisions
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PPP5_HUMAN PPP5_HUMAN]] May play a role in the regulation of RNA biogenesis and/or mitosis. In vitro, dephosphorylates serine residues of skeletal muscle phosphorylase and histone H1. | [[http://www.uniprot.org/uniprot/PPP5_HUMAN PPP5_HUMAN]] May play a role in the regulation of RNA biogenesis and/or mitosis. In vitro, dephosphorylates serine residues of skeletal muscle phosphorylase and histone H1. | ||
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== Publication Abstract from PubMed == | |||
The serine/threonine phosphatase protein phosphatase 5 (PP5) regulates hormone- and stress-induced cellular signaling by association with the molecular chaperone heat shock protein 90 (Hsp90). PP5-mediated dephosphorylation of the cochaperone Cdc37 is essential for activation of Hsp90-dependent kinases. However, the details of this mechanism remain unknown. We determined the crystal structure of a Cdc37 phosphomimetic peptide bound to the catalytic domain of PP5. The structure reveals PP5 utilization of conserved elements of phosphoprotein phosphatase (PPP) structure to bind substrate and provides a template for many PPP-substrate interactions. Our data show that, despite a highly conserved structure, elements of substrate specificity are determined within the phosphatase catalytic domain itself. Structure-based mutations in vivo reveal that PP5-mediated dephosphorylation is required for kinase and steroid hormone receptor release from the chaperone complex. Finally, our data show that hyper- or hypoactivity of PP5 mutants increases Hsp90 binding to its inhibitor, suggesting a mechanism to enhance the efficacy of Hsp90 inhibitors by regulation of PP5 activity in tumors. | |||
Structural and functional basis of protein phosphatase 5 substrate specificity.,Oberoi J, Dunn DM, Woodford MR, Mariotti L, Schulman J, Bourboulia D, Mollapour M, Vaughan CK Proc Natl Acad Sci U S A. 2016 Jul 27. pii: 201603059. PMID:27466404<ref>PMID:27466404</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | |||
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</StructureSection> | </StructureSection> | ||