# name
The E3 ubiquitin protein ligase HERC2 modulates the activity of tumor protein p53 by regulating its oligomerization

# metadata.dc.description.abstract[].value
The tumor suppressor p53 is a transcription factor that coordinates the cellular response to several kinds of stress. p53 inactivation is an important step in tumor progression. Oligomerization of p53 is critical for its post-translational modification and its ability to regulate the transcription of target genes necessary to inhibit tumor growth. Here, we report that the HECT E3 ubiquitin ligase HERC2 interacts with p53. This interaction involves the CPH domain of HERC2 and the last 43 amino acid residues of p53. Through this interaction, HERC2 regulates p53 activity. RNA interference experiments showed how HERC2 depletion reduces the transcriptional activity of p53 without affecting its stability. This regulation of p53 activity by HERC2 is independent of proteasome or MDM2 activity. Under these conditions, upregulation of cell growth and increased focus formation were observed, showing the functional relevance of the HERC2/p53 interaction. This interaction was maintained after DNA damage caused by the chemotherapeutic drug bleomycin. In these stressed cells, p53 phosphorylation was not impaired by HERC2 knockdown. Interestingly, p53 mutations that affect its tetramerization domain disrupted the HERC2/p53 interaction suggesting a role for HERC2 in p53 oligomerization. This regulatory role was shown using cross-linking assays. Thus, the inhibition of p53 activity after HERC2 depletion can be attributed to a reduction in p53 oligomerization. Ectopic expression of HERC2 (residues 2292 to 2923) confirmed these observations. Altogether, these results identify HERC2 as a novel regulator of p53 signaling.

# metadata.dc.publisher[].value
American Society for Biochemistry and Molecular Biology

# metadata.dc.rights[].value
(c) American Society for Biochemistry and Molecular Biology, 2014

# metadata.dc.source[].value
Articles publicats en revistes (Ciències Fisiològiques)

# metadata.dc.title[].value
The E3 ubiquitin protein ligase HERC2 modulates the activity of tumor protein p53 by regulating its oligomerization