V-Rel Reticuloendotheliosis Viral Oncogene Homolog (REL)

The REL gene encodes c-Rel, a transcription factor that is a member of the Rel/NFKB family, which also includes RELA, RELB, NFKB1, and NFKB2. These proteins are related through a highly conserved N-terminal region termed the 'Rel domain,' which is responsible for DNA binding, dimerization, nuclear localization, and binding to the NFKB inhibitor.Further studies identified protein kinase C-theta (PRKCQ) as a positive regulator of c-Rel transcriptional activity, as well as downstream target genes. In human breast cancer cell lines, there was an inverse correlation between ESR1 and PRKCQ mRNA, and PRKCQ was found to inhibit ESR1 expression via activation of AKT1. PRKCQ plays a pivotal role in mammary tumorigenesis by activating AKT, which ultimately leads to derepression of c-Rel through inhibition of ESR1.