• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Regulation of p53 localization and activity by Ubc13.

The abundance and activity of p53 are regulated largely by ubiquitin ligases. Here we demonstrate a previously undisclosed regulation of p53 localization and activity by Ubc13, an E2 ubiquitin-conjugating enzyme. While increasing p53 stability, Ubc13 decreases p53 transcriptional activity and increases its localization to the cytoplasm, changes that require its ubiquitin-conjugating activity. Ubc13 elicits K63-dependent ubiquitination of p53, which attenuates Hdm2-induced polyubiquitination of p53. Ubc13 association with p53 requires an intact C-terminal domain of p53 and is markedly stronger with a p53 mutant that cannot tetramerize. Expression of Ubc13 in vivo increases the pool of monomeric p53, indicating that Ubc13 affects tetramerization of p53. Significantly, wild-type but not mutant Ubc13 is associated with polysomes and enriches p53 within this fraction. In response to DNA damage, Ubc13 is no longer capable of facilitating p53 monomerization, in part due to a decrease in its own levels which is p53 dependent. Our findings point to a newly discerned mechanism important in the regulation of p53 organization, localization, and activity by Ubc13.

Pubmed ID: 17000756

Authors

  • Laine A
  • Topisirovic I
  • Zhai D
  • Reed JC
  • Borden KL
  • Ronai Z

Journal

Molecular and cellular biology

Publication Data

December 19, 2006

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 69381
  • Agency: NCI NIH HHS, Id: CA 78419
  • Agency: NCI NIH HHS, Id: R01 CA078419

Mesh Terms

  • Animals
  • Cells, Cultured
  • Female
  • Fibroblasts
  • Gene Expression Regulation
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Mutation
  • Pregnancy
  • Protein Binding
  • Protein Structure, Tertiary
  • Tumor Suppressor Protein p53
  • Ubiquitin-Conjugating Enzymes