Death-Associated Protein Kinase 1 Phosphorylates Pin1 and Inhibits Its Prolyl Isomerase Activity and Cellular Function
Open accessAbstract
Pin1 is a phospho-specific prolyl isomerase that regulates numerous key signaling molecules and whose deregulation contributes to disease notably cancer. However, since prolyl isomerases are often believed to be constitutively active, little is known whether and how Pin1 catalytic activity is regulated. Here, we identify death-associated protein kinase 1 (DAPK1), a known tumor suppressor, as a kinase responsible for phosphorylation of Pin1 on Ser71 in the catalytic active site. Such phosphorylation fully inactivates Pin1 catalytic activity and inhibits its nuclear location. Moreover, DAPK1 inhibits the ability of Pin1 to induce centrosome amplification and cell transformation. Finally, Pin1 pSer71 levels are positively correlated with DAPK1 levels and negatively with centrosome amplification in human breast cancer. Thus, phosphorylation of Pin1 Ser71 by DAPK1 inhibits its catalytic activity and cellular function, providing strong evidence for an essential role of the Pin1 enzymatic activity for its cellular function.
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UV irradiation induces DAPK1 to phosphorylate Pin1 at Ser71, inactivating its isomerase activity.
“UV irradiation induces DAPK1 to phosphorylate Pin1 at Ser71, thus inactivating the isomerase activity 49, 50.”
From Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation (2017) · cites this paper as [50]
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- Authors
- Lee, T. H., Chen, C.-H., Suizu, F., Huang, P., Schiene-Fischer, C., Daum, S., Zhang, Y. J., Goate, A., Chen, R.-H., Zhou, X. Z., & Lu, K. P.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Max Planck Research Unit for Enzymology of Protein Folding (DE)
- The University of Texas at Austin (US)
- Washington University in St. Louis (US)
- Institute of Biological Chemistry, Academia Sinica (TW)
- Corresponding author
- Lu, Kun Ping
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 42
- Issue
- 2
- Pages
- 147-159
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3088080
- OpenAlex
- W2041352318
- Cited by
- 183
- References
- 47
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 23 · 2023: 10 · 2022: 8 · 2021: 8 · 2020: 16 · 2019: 10 · 2018: 15 · 2017: 11 · 2016: 17 · 2015: 15 · 2014: 12 · 2013: 13 · 2012: 10
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- National Institute on Aging (R01AG017870, K99AG033104)
- National Cancer Institute (R01CA122434)
- National Institute of General Medical Sciences (R01GM058556, R01 GM 56230, R01GM056230)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Keywords
- Pin1, DAPK1, peptidyl-prolyl isomerase, protein phosphorylation, catalytic activity regulation, centrosome amplification, cell transformation, breast cancer, nuclear localization, tumor suppressor
- MeSH terms
- NIMA-Interacting Peptidylprolyl Isomerase, Animals, Breast Neoplasms, Cell Cycle, Cell Nucleus, Cell Transformation, Neoplastic, Enzyme Stability, Female, HeLa Cells, Humans, Immunohistochemistry, Microscopy, Fluorescence, Mutation, Phosphorylation, Recombinant Fusion Proteins, Serine, Time Factors, Transfection, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, Mice, Knockout, Centrosome, Peptidylprolyl Isomerase, Catalytic Domain, Active Transport, Cell Nucleus, Protein Interaction Mapping, NIH 3T3 Cells, Tissue Array Analysis, Cell Proliferation, Apoptosis Regulatory Proteins, Mice, Protein Interaction Domains and Motifs, Death-Associated Protein Kinases
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