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Publication : Regulatory feedback loop between TP73 and TRIM32.

First Author  Gonzalez-Cano L Year  2013
Journal  Cell Death Dis Volume  4
Pages  e704 PubMed ID  23828567
Mgi Jnum  J:318672 Mgi Id  MGI:6858581
Doi  10.1038/cddis.2013.224 Citation  Gonzalez-Cano L, et al. (2013) Regulatory feedback loop between TP73 and TRIM32. Cell Death Dis 4:e704
abstractText  The p73 transcription factor is one of the members of the p53 family of tumor suppressors with unique biological functions in processes like neurogenesis, embryonic development and differentiation. For this reason, p73 activity is tightly regulated by multiple mechanisms, including transcription and post-translational modifications. Here, we identified a novel regulatory loop between TAp73 and the E3 ubiquitin ligase tripartite motif protein 32 (TRIM32). TRIM32, a new direct p73 transcriptional target in the context of neural progenitor cells, is differentially regulated by p73. Although TAp73 binds to the TRIM32 promoter and activates its expression, TAp73-induced TRIM32 expression is efficiently repressed by DNp73. TRIM32 in turn physically interacts with TAp73 and promotes its ubiquitination and degradation, impairing p73-dependent transcriptional activity. This mutual regulation between p73 and TRIM32 constitutes a novel feedback loop, which might have important implications in central nervous system development as well as relevance in oncogenesis, and thus emerges as a possible therapeutic target.
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