Death-Associated Protein Kinase 1 Phosphorylates Pin1 and Inhibits Its Prolyl Isomerase Activity and Cellular Function

Tae Ho Lee, Chun Hau Chen, Futoshi Suizu, Pengyu Huang, Cordelia Schiene-Fischer, Sebastian Daum, Yan Jessie Zhang, Alison Goate, Ruey Hwa Chen, Xiao Zhen Zhou, Kun Ping Lu

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)147-159
Number of pages13
JournalMolecular Cell
Volume42
Issue number2
DOIs
StatePublished - 22 Apr 2011
Externally publishedYes

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