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Updated: Aug 19, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
Down-regulation of UCRP and UBE2L6 in BRCA2 knocked-down human breast cells
Manish K Tripathi1, Gautam Chaudhuri
1Department of Microbiology, Meharry Medical College, Nashville, TN 37208, USA.
Abstract:
To understand the effects of the transient ablation of BRCA2 gene expression in dividing human breast cells, we transiently knocked down BRCA2 mRNA in HMEC and other cells. Microarray analysis of mRNAs revealed the down-regulation of the mRNAs of ubiquitin cross-reacting protein (UCRP) and the E2 enzyme that help conjugating UCRP to its target proteins, namely UBE2L6 (UbcH8), in BRCA2 ablated cells. UCRP is an interferon regulated protein, involved in cell growth and cell cycle events by participating in the degradation/modulation of cell cycle regulatory proteins. Quantitative-PCR and Northern analysis confirmed down-regulation of UCRP and UBE2L6 with BRCA2 knockdown, respectively. Since UCRP and UCRPylation have critical roles in the innate immunity against viral infection and during pregnancy, our observation may indicate new roles of the BRCA2 protein.
Insights
BRCA2 gene knockdown in human breast cells reduced ubiquitin cross-reacting protein (UCRP) and UBE2L6 expression. This suggests BRCA2 may influence cell growth and innate immunity pathways.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- BRCA2 is crucial for DNA repair and maintaining genomic stability.
- Its role in regulating gene expression beyond DNA repair is less understood.
Purpose of the Study:
- To investigate the impact of BRCA2 gene ablation on mRNA expression in human breast cells.
- To identify specific genes affected by BRCA2 knockdown.
Main Methods:
- Transient knockdown of BRCA2 mRNA in HMEC and other human breast cell lines.
- Microarray analysis to profile mRNA expression changes.
- Quantitative-PCR and Northern blot analysis for validation.
Main Results:
- BRCA2 knockdown led to the down-regulation of ubiquitin cross-reacting protein (UCRP) mRNA.
- The expression of UBE2L6 (UbcH8), an E2 enzyme involved in UCRP conjugation, was also reduced.
- UCRP, an interferon-regulated protein, plays roles in cell growth and cell cycle regulation.
Conclusions:
- BRCA2 gene expression influences the regulation of UCRP and UBE2L6.
- These findings suggest potential novel roles for BRCA2 in cell cycle control and innate immunity.
- Further research into UCRPylation pathways may reveal new functions of BRCA2.
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