Int J Biol Sci 2022; 18(11):4316-4328. doi:10.7150/ijbs.69466 This issue Cite

Research Paper

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

Guimei Cui1,2,3,6, Zhuoran Gao1,2,3,6, Shiehong Chang1,2,6, Nitin Narwade1,2,3,6, Yitian Chen1,2,3,6, Barun Poudel1,2,6, Kate M. K. Lei1,2,3,4,5,6, Weibo Zhang1,2,3,6, Gang Li1,2,3,6, Terence C. W. Poon1,2,3,4,5,6, Edwin Cheung1,2,3,6✉

1. Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China.
2. Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China.
3. MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, China.
4. Pilot Laboratory, University of Macau, Macau SAR, China.
5. Institute of Translational Medicine, University of Macau, Macau SAR, China.
6. Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.

Citation:
Cui G, Gao Z, Chang S, Narwade N, Chen Y, Poudel B, Lei KMK, Zhang W, Li G, Poon TCW, Cheung E. TRIM37 Augments AP-2γ Transcriptional Activity and Cellular Localization via K63-linked Ubiquitination to Drive Breast Cancer Progression. Int J Biol Sci 2022; 18(11):4316-4328. doi:10.7150/ijbs.69466. https://www.ijbs.com/v18p4316.htm
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Abstract

Graphic 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.

Keywords: AP-2γ, TRIM37, breast cancer, transcriptional regulation


Citation styles

APA
Cui, G., Gao, Z., Chang, S., Narwade, N., Chen, Y., Poudel, B., Lei, K.M.K., Zhang, W., Li, G., Poon, T.C.W., Cheung, E. (2022). TRIM37 Augments AP-2γ Transcriptional Activity and Cellular Localization via K63-linked Ubiquitination to Drive Breast Cancer Progression. International Journal of Biological Sciences, 18(11), 4316-4328. https://doi.org/10.7150/ijbs.69466.

ACS
Cui, G.; Gao, Z.; Chang, S.; Narwade, N.; Chen, Y.; Poudel, B.; Lei, K.M.K.; Zhang, W.; Li, G.; Poon, T.C.W.; Cheung, E. TRIM37 Augments AP-2γ Transcriptional Activity and Cellular Localization via K63-linked Ubiquitination to Drive Breast Cancer Progression. Int. J. Biol. Sci. 2022, 18 (11), 4316-4328. DOI: 10.7150/ijbs.69466.

NLM
Cui G, Gao Z, Chang S, Narwade N, Chen Y, Poudel B, Lei KMK, Zhang W, Li G, Poon TCW, Cheung E. TRIM37 Augments AP-2γ Transcriptional Activity and Cellular Localization via K63-linked Ubiquitination to Drive Breast Cancer Progression. Int J Biol Sci 2022; 18(11):4316-4328. doi:10.7150/ijbs.69466. https://www.ijbs.com/v18p4316.htm

CSE
Cui G, Gao Z, Chang S, Narwade N, Chen Y, Poudel B, Lei KMK, Zhang W, Li G, Poon TCW, Cheung E. 2022. TRIM37 Augments AP-2γ Transcriptional Activity and Cellular Localization via K63-linked Ubiquitination to Drive Breast Cancer Progression. Int J Biol Sci. 18(11):4316-4328.

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