Negative regulation of BRCA1 by transforming acidic coiled-coil protein 3 (TACC3)
| Autor: | Eun-Kyoung Breuer, Loredana Campo, Geun-Hyoung Ha, Jung-Lye Kim |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genome instability Ubiquitin-Protein Ligases Biophysics Breast Neoplasms Biology medicine.disease_cause Biochemistry Genomic Instability Cell Line law.invention 03 medical and health sciences Breast cancer law BARD1 Gene expression medicine Humans Protein Interaction Maps Epigenetics skin and connective tissue diseases Molecular Biology Mitosis BRCA1 Protein Protein Stability Tumor Suppressor Proteins Ubiquitination Cell Biology medicine.disease 030104 developmental biology Proteolysis Cancer research Suppressor Female Carcinogenesis Microtubule-Associated Proteins |
| Zdroj: | Biochemical and Biophysical Research Communications. 496:633-640 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2018.01.101 |
| Popis: | In spite of the push to identify modifiers of BRCAness, it still remains unclear how tumor suppressor BRCA1 is lost in breast cancers in the absence of genetic or epigenetic aberrations. Mounting evidence indicates that the transforming acidic coiled-coil 3 (TACC3) plays an important role in the centrosome-microtubule network during mitosis and gene expression, and that deregulation of TACC3 is associated with breast cancer. However, the molecular mechanisms by which TACC3 contributes to breast cancer development have yet to be elucidated. Herein, we found that high levels of TACC3 in human mammary epithelial cells can cause genomic instability possibly in part through destabilizing BRCA1. We also found that high levels of TACC3 inhibited the interaction between BRCA1 and BARD1, thus subsequently allowing the BARD1-uncoupled BRCA1 to be destabilized by ubiquitin-mediated proteosomal pathway. Moreover, there is an inverse correlation between TACC3 and BRCA1 expression in breast cancer tissues. Overall, our findings provide a new insight into the role of TACC3 in genomic instability and breast tumorigenesis. |
| Databáze: | OpenAIRE |
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