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.
Nikolaev
Anatoly Y
AY
Institute for Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.
Li
Muyang
M
Puskas
Norbert
N
Qin
Jun
J
Gu
Wei
W
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; D005047:Etoposide; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D005982:Glutathione Transferase; D008025:Ligases