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

Activator Protein 2 gamma (AP-2?) 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?-mediated transcription in breast ...
cancer cells. We demonstrate that TRIM37 facilitates AP-2? chromatin binding to directly regulate the AP-2? mediated transcriptional program. We also show that TRIM37 achieves this by stimulating K63 chain-linked ubiquitination of AP-2?, 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? interaction is essential for breast cancer tumor growth. Overall, our work reveals that TRIM37 is an oncogenic coactivator of AP-2? in breast cancer and provides a novel therapeutic target for treating the disease.
Mesh Terms:
Breast Neoplasms, Female, Gene Expression Regulation, Humans, Transcription Factor AP-2, Transcription Factors, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Ubiquitination
Int J Biol Sci
Date: Jul. 23, 2022
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