Mapping the Subtype-Specific PARP1 ADP-ribosylated Proteome in Breast Cancer Cells - PubMed
4 hours ago
- #ADP-ribosylation
- #PARP1
- #breast cancer
- Breast cancers show subtype-specific differences in gene expression and therapeutic responses.
- PARP1's catalytic activity extends beyond DNA repair to include gene regulation.
- Using NAD analog-sensitive PARP1 and mass spectrometry, the ADP-ribosylated proteome was mapped across six breast cancer cell lines.
- Thousands of PARP1 substrates and hundreds of Glu/Asp ADPRylation sites were identified, revealing shared and subtype-specific modifications.
- Luminal-specific substrates are enriched in chromatin and transcriptional regulators, while basal-specific substrates are linked to translation and RNA processing.
- Transcription factors, like TFAP2A, are major substrates; inhibition of ADPRylation alters TFAP2A promoter occupancy in a subtype-specific manner.
- Findings expand PARP1's role beyond DNA repair, offering insights into subtype-specific gene regulation and PARP inhibitor sensitivity.