1. Parc: A Cytoplasmic Anchor for p53
- Author
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Nikolaev, Anatoly Y., Li, Muyang, Puskas, Norbert, Qin, Jun, and Gu, Wei
- Subjects
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TUMOR suppressor proteins , *CYTOPLASM - Abstract
Nuclear localization of p53 is essential for its tumor suppressor function. Here, we have identified Parc, a Parkin-like ubiquitin ligase, as a cytoplasmic anchor protein in p53-associated protein complexes. Parc directly interacts and forms a ∼1 MDa complex with p53 in the cytoplasm of unstressed cells. In the absence of stress, inactivation of Parc induces nuclear localization of endogenous p53 and activates p53-dependent apoptosis. Overexpression of Parc promotes cytoplasmic sequestration of ectopic p53. Furthermore, abnormal cytoplasmic localization of p53 was observed in a number of neuroblastoma cell lines; RNAi-mediated reduction of endogenous Parc significantly sensitizes these neuroblastoma cells in the DNA damage response. These results reveal that Parc is a critical regulator in controlling p53 subcellular localization and subsequent function. [Copyright &y& Elsevier]
- Published
- 2003
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