ArticleThe Journal of biological chemistry2011
Disruption of serine/threonine protein phosphatase 5 (PP5:PPP5c) in mice reveals a novel role for PP5 in the regulation of ultraviolet light-induced phosphorylation of serine/threonine protein kinase Chk1 (CHEK1).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- SUMOylation of protein phosphatase 5 regulates phosphatase activity and substrate release.EMBO reports · 2024Article
- Hsp90 provides a platform for kinase dephosphorylation by PP5.Nature communications · 2023Article
- Plk4 Is a Novel Substrate of Protein Phosphatase 5.International journal of molecular sciences · 2023Article
- Multi-Level Control of the ATM/ATR-CHK1 Axis by the Transcription Factor E4F1 in Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Article
- Functional analysis of a novel de novo variant in PPP5C associated with microcephaly, seizures, and developmental delay.Molecular genetics and metabolism · 2022Article
- MicroRNA-365b-3p represses the proliferation and promotes the apoptosis of non-small cell lung cancer cells by targeting PPP5C.Oncology letters · 2021Article
- Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders.Frontiers in molecular biosciences · 2021Review
- Structure and function of the co-chaperone protein phosphatase 5 in cancer.Cell stress & chaperones · 2020Review
- Cuminal InhibitsMicroorganisms · 2020Article
- Cell Cycle and DNA Repair Regulation in the Damage Response: Protein Phosphatases Take Over the Reins.International journal of molecular sciences · 2020Review
- The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C.Molecular cancer therapeutics · 2019Article
- Protein phosphatase 5 and the tumor suppressor p53 down-regulate each other's activities in mice.The Journal of biological chemistry · 2018Article
- Knockdown of serine/threonine protein phosphatase 5 enhances gemcitabine sensitivity by promoting apoptosis in pancreatic cancer cellsOncology letters · 2018Article
- The activity of protein phosphatase 5 towards native clients is modulated by the middle- and C-terminal domains of Hsp90.Scientific reports · 2015Article
- Insights into the key interactions between human protein phosphatase 5 and cantharidin using molecular dynamics and site-directed mutagenesis bioassays.Scientific reports · 2015Article
- Genetic analysis of litter size in mice.The Journal of veterinary medical science · 2015Article
- Protein phosphatases in pancreatic islets.The Journal of endocrinology · 2014Review
- Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5)·extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1.The Journal of biological chemistry · 2014Article
- Response to DNA damage: why do we need to focus on protein phosphatases?Frontiers in oncology · 2013Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
PP5 is a ubiquitously expressed Ser/Thr protein phosphatase. High levels of PP5 have been observed in human cancers, and constitutive PP5 overexpression aids tumor progression in mouse models of tumor development. However, PP5 is highly conserved among species, and the roles of PP5 in normal tissues are not clear. Here, to help evaluate the biological actions of PP5, a Cre/loxP-conditional mouse line was generated. In marked contrast to the early embryonic lethality associated with the genetic disruption of other PPP family phosphatases (e.g. PP2A and PP4), intercrosses with mouse lines that ubiquitously express Cre recombinase starting early in development (e.g. MeuCre40 and ACTB-Cre) produced viable and fertile PP5-deficient mice. Phenotypic differences caused by the total disruption of PP5 were minor, suggesting that small molecule inhibitors of PP5 will not have widespread systemic toxicity. Examination of roles for PP5 in fibroblasts generated from PP5-deficient embryos (PP5(-/-) mouse embryonic fibroblasts) confirmed some known roles and identified new actions for PP5. PP5(-/-) mouse embryonic fibroblasts demonstrated increased sensitivity to UV light, hydroxyurea, and camptothecin, which are known activators of ATR (ataxia-telangiectasia and Rad3-related) kinase. Further study revealed a previously unrecognized role for PP5 downstream of ATR activation in a UV light-induced response. The genetic disruption of PP5 is associated with enhanced and prolonged phosphorylation of a single serine (Ser-345) on Chk1, increased phosphorylation of the p53 tumor suppressor protein (p53) at serine 18, and increased p53 protein levels. A comparable role for PP5 in the regulation of Chk1 phosphorylation was also observed in human cells.
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