Parc: a cytoplasmic anchor for p53

Cell. 2003 Jan 10;112(1):29-40. doi: 10.1016/s0092-8674(02)01255-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Apoptosis
  • Cell Nucleus / metabolism
  • Cytoplasm / enzymology
  • Cytoplasm / metabolism*
  • Cytoplasm / physiology
  • Etoposide / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Glutathione Transferase / metabolism
  • Humans
  • Ligases* / chemistry
  • Ligases* / metabolism
  • Ligases* / physiology
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • 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
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin-Protein Ligases*
  • Ubiquitins / metabolism


  • Neoplasm Proteins
  • Nucleic Acid Synthesis Inhibitors
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Ubiquitins
  • Etoposide
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Glutathione Transferase
  • Ligases