1. Parc: a cytoplasmic anchor for p53.
- Author
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Nikolaev AY, Li M, Puskas N, Qin J, and Gu W
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Apoptosis, Cell Nucleus metabolism, Cytoplasm enzymology, Cytoplasm physiology, Etoposide pharmacology, Gene Expression Regulation, Neoplastic, Glutathione Transferase metabolism, Humans, Molecular Sequence Data, Neoplasm Proteins chemistry, Neoplasm Proteins physiology, Nucleic Acid Synthesis Inhibitors pharmacology, Protein Structure, Tertiary, RNA, Small Interfering metabolism, Sequence Homology, Amino Acid, Tumor Cells, Cultured, Tumor Suppressor Protein p53 chemistry, Ubiquitins metabolism, Cytoplasm metabolism, Ligases chemistry, Ligases metabolism, Ligases physiology, Neoplasm Proteins metabolism, Tumor Suppressor Protein p53 metabolism, Ubiquitin-Protein Ligases
- 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 approximately 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.
- Published
- 2003
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