Parc: a cytoplasmic anchor for p53.
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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Apoptosis, Cell Nucleus, Cytoplasm, Etoposide, Gene Expression Regulation, Neoplastic, Glutathione Transferase, Humans, Ligases, Molecular Sequence Data, Neoplasm Proteins, Nucleic Acid Synthesis Inhibitors, Protein Structure, Tertiary, RNA, Small Interfering, Sequence Homology, Amino Acid, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, Ubiquitins
Amino Acid Motifs, Amino Acid Sequence, Apoptosis, Cell Nucleus, Cytoplasm, Etoposide, Gene Expression Regulation, Neoplastic, Glutathione Transferase, Humans, Ligases, Molecular Sequence Data, Neoplasm Proteins, Nucleic Acid Synthesis Inhibitors, Protein Structure, Tertiary, RNA, Small Interfering, Sequence Homology, Amino Acid, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, Ubiquitins
Cell
Date: Jan. 10, 2003
PubMed ID: 12526791
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