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TRIM25 targets p300 for degradation.

Seham Elabd1,2, Eleonora Pauletto1, Valeria Solozobova3

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The E3 ubiquitin ligase TRIM25 targets the transcriptional co-activator p300 for degradation. This process involves dynein-mediated transport to proteasomes, impacting gene expression and cellular homeostasis.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • p300 is a crucial transcriptional co-activator involved in regulating gene expression, cell proliferation, and cell division.
  • The precise mechanisms governing p300 regulation and its cellular homeostasis are not fully understood.
  • TRIM25 is a member of the tripartite motif (TRIM) protein family with known roles in various cellular processes.

Purpose of the Study:

  • To elucidate the regulatory mechanisms controlling the stability and function of the transcriptional co-activator p300.
  • To investigate the role of TRIM25 in the regulation of p300.
  • To understand how TRIM25 influences p300-dependent cellular processes.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Western blotting to assess protein levels and degradation.
  • Immunofluorescence microscopy to visualize protein localization and transport.
  • Ubiquitination assays to examine post-translational modifications.

Main Results:

  • TRIM25 targets p300 for proteasomal degradation.
  • p300 degradation by TRIM25 is independent of direct ubiquitination of p300 by TRIM25.
  • TRIM25 facilitates the interaction between p300 and dynein, a motor protein involved in intracellular transport.
  • This interaction leads to microtubule-dependent transport of p300 to cellular proteasomes for degradation.
  • TRIM25-mediated p300 degradation influences p300-dependent gene expression patterns.

Conclusions:

  • TRIM25 acts as a negative regulator of p300 stability through a novel non-ubiquitinating mechanism.
  • TRIM25 controls p300 levels via dynein-mediated transport to proteasomes, impacting cellular processes.
  • This finding reveals a new layer of regulation for p300, essential for maintaining cellular homeostasis and gene expression.