TRIM37 Augments AP-2γ Transcriptional Activity and Cellular Localization via K63-linked Ubiquitination to Drive Breast Cancer Progression

Activator Protein 2 gamma (AP-2 gamma) is a master transcription factor that plays a critical role in the development and progression of breast cancer. However, the underlying mechanism is still unclear. Herein, using a proteomics approach, we identified Tripartite motif-containing 37 (TRIM37) as a novel coactivator of AP-2 gamma-mediated transcription in breast cancer cells. We demonstrate that TRIM37 facilitates AP-2 gamma chromatin binding to directly regulate the AP-2 gamma mediated transcriptional program. We also show that TRIM37 achieves this by stimulating K63 chain-linked ubiquitination of AP-2 gamma, promoting protein localization from the cytoplasm to the nucleus. In clinical analyses, we find TRIM37 is upregulated in multiple breast cancer datasets, supporting our findings that the TRIM37-AP-2 gamma interaction is essential for breast cancer tumor growth. Overall, our work reveals that TRIM37 is an oncogenic coactivator of AP-2 gamma in breast cancer and provides a novel therapeutic target for treating the disease.

Automated summary

This study identifies TRIM37 as a novel coactivator of AP-2 gamma in breast cancer cells and demonstrates its role in regulating transcription by promoting K63 chain-linked ubiquitination of AP-2 gamma.