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

Abstract

Activator Protein 2 gamma (AP-2γ) 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-2γ-mediated transcription in breast cancer cells. We demonstrate that TRIM37 facilitates AP-2γ chromatin binding to directly regulate the AP-2γ mediated transcriptional program. We also show that TRIM37 achieves this by stimulating K63 chain-linked ubiquitination of AP-2γ, 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-2γ interaction is essential for breast cancer tumor growth. Overall, our work reveals that TRIM37 is an oncogenic coactivator of AP-2γ in breast cancer and provides a novel therapeutic target for treating the disease.

Inhibition of UFM1 expression suppresses cancer progression and is linked to the dismal prognosis and immune infiltration in oral squamous cell carcinoma

“…We found that UFM1 is associated with the ubiquitinating genes: CDC73, RNF2, BMI1, RAG1, PCGF3, PCGF6, TRIM37, PAF1, CTR9, RYBP, CUL4B, PCGF1, PCGF2, UBE2E1, RNF40, WAC, UHRF1, and PCGF5 levels. Studies have depicted that RNF2, BMI1, TRIM37, and other ubiquitinating genes were related to cancer progression [20][21][22][23][24]. These results further suggested that the ubiquitin-like protein UFM1 has an important role in OSCC progression.…”

Emerging roles of tripartite motif family proteins (TRIMs) in breast cancer

“… 145 SUMOylation of TRIM24 promotes cell adhesion to extracellular matrix proteins, including fibronectin, laminin, and tenascin, thereby regulating cell adhesion. 178 TRIM25 was proposed to be a potent pro‐metastatic transcription factor, 179 while cumulative results provided compelling evidence that TRIM14, 180 TRIM27, 181 TRIM28, 182 TRIM37, 114 and TRIM59 183 are also carcinogenic hallmarks in BC.…”

Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views

“…Tripartite motif-containing 37 (TRIM37) facilitates TFAP2C-mediated transcriptional activity on ERα in breast cancer. TRIM37 induces K63 chain-linked ubiquitination of TFAP2C, which facilitates the translocation of TFAP2C to the nucleus from the cytoplasm [ 23 ]. Furthermore, TFAP2C interacts with the signal transducer and activator of transcription 3 (STAT3) to form the TFAP2C/STAT3 complex and thus perturbs STAT3 phosphorylation, which prevents phosphorylated STAT3 from entering the nucleus to trigger fucosyltransferase 8 ( FUT8 ) transcription [ 24 ].…”