TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Tripartite Motif-Containing Protein 24 (TRIM24) stabilization is observed in prostate cancer (PCa) with SPOP mutations.
• Mechanisms regulating TRIM24 in SPOP-wildtype PCa remain largely unknown.

Purpose of the Study:

• To identify upstream regulators of TRIM24 in prostate cancer.
• To elucidate the role of TRIM28 in TRIM24 protein stabilization and its impact on PCa progression.

Main Methods:

• Co-immunoprecipitation assays to assess protein interactions.
• Western blotting to evaluate protein levels and ubiquitination.
• Chromatin immunoprecipitation to determine target gene occupancy.
• In vitro cell proliferation assays and in vivo xenograft models to assess tumor growth.

Main Results:

• TRIM28 directly interacts with TRIM24, inhibiting its ubiquitination and SPOP-mediated degradation.
• TRIM28 enhances TRIM24's chromatin occupancy and androgen receptor (AR) signaling.
• TRIM28 promotes PCa cell proliferation and tumor growth.
• TRIM28 is upregulated in aggressive PCa, correlating with elevated TRIM24 and poor clinical outcomes.

Conclusions:

• TRIM28 acts as a critical upstream regulator, stabilizing TRIM24 protein through a novel mechanism.
• TRIM28 is implicated in promoting PCa progression and represents a potential therapeutic target for aggressive disease.