RBPJ
Overview
RBPJ (Recombination Signal Binding Protein for Immunoglobulin Kappa J Region; also CSL) is the canonical transcriptional effector of Notch signaling. In the presence of activated Notch intracellular domain (NICD), RBPJ switches from a transcriptional repressor to an activator of Notch target genes. In adenoid cystic carcinoma (ACC), the RBPJ/Notch motif is specifically enriched at grade-3-specific enhancers, linking Notch pathway activation to high-grade disease and suggesting RBPJ as a mediator of aggressive ACC biology.
Alterations observed in the corpus
- RBPJ/Notch binding motif significantly enriched at grade-3-specific enhancers in ACC (WGS + H3K27ac ChIP-seq; n=20 tumors); enrichment indicates Notch-pathway transcriptional activation in high-grade ACC PMID:26829750
Cancer types (linked)
- ACYC (adenoid cystic carcinoma): RBPJ motif enrichment at grade-3-specific enhancers identifies Notch as a dominant transcriptional program driving high-grade progression; NOTCH1 is also the most-frequently mutated gene in the ACC WGS cohort PMID:26829750
Co-occurrence and mutual exclusivity
- RBPJ/Notch motif enrichment co-occurs with NOTCH1 point mutations and structural activating alterations in high-grade ACC; RBPJ acts downstream of activated NOTCH1 intracellular domain PMID:26829750
Therapeutic relevance
- Notch pathway (via RBPJ) is identified as a major transcriptional axis in grade-3 ACC; gamma-secretase inhibitors and other Notch-targeted agents are potential therapeutic candidates, though no treatment data are reported in this study PMID:26829750
Open questions
- Whether RBPJ is directly mutated or only activated by upstream NOTCH1 alterations in ACC requires further characterization; functional experiments validating RBPJ-dependent transcription in ACC models are not presented.
Sources
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