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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Regulatory feedback loop between TP73 and TRIM32
L Gonzalez-Cano1, A-L Hillje, S Fuertes-Alvarez
1Instituto de Biomedicina (IBIOMED), Department of Molecular Biology, Universidad de León, Campus de Vegazana, León 24071, Spain.
Abstract:
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.
Insights
The p73 transcription factor and TRIM32 form a novel feedback loop regulating neural development and cancer. This interaction impacts p73 activity, offering potential therapeutic targets for central nervous system disorders and oncogenesis.
Area of Science:
- Molecular Biology
- Neuroscience
- Oncology
Background:
- The p73 transcription factor, a member of the p53 family, plays crucial roles in neurogenesis, embryonic development, and differentiation.
- p73 activity is regulated by multiple mechanisms, including transcriptional and post-translational modifications.
Purpose of the Study:
- To identify and characterize a novel regulatory loop involving TAp73 and the E3 ubiquitin ligase TRIM32.
- To elucidate the functional implications of this p73-TRIM32 interaction in neural progenitor cells and its relevance to oncogenesis.
Main Methods:
- Investigated the transcriptional regulation of TRIM32 by p73, including TAp73 activation and DNp73 repression.
- Examined the physical interaction between TRIM32 and TAp73.
- Assessed the effect of TRIM32 on TAp73 ubiquitination, degradation, and transcriptional activity.
Main Results:
- TRIM32 is identified as a direct transcriptional target of p73 in neural progenitor cells.
- TRIM32 physically interacts with TAp73, promoting its ubiquitination and degradation.
- This interaction impairs TAp73-dependent transcriptional activity, establishing a feedback loop.
Conclusions:
- A novel feedback regulatory loop between p73 and TRIM32 is identified, impacting p73 activity.
- This loop has significant implications for central nervous system development and oncogenesis.
- The p73-TRIM32 axis represents a potential therapeutic target for related diseases.
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