Regulation of stability and inhibitory activity of the tumor suppressor SEF through casein-kinase II-mediated phosphorylation.

Inflammation and cancer are intimately linked. A key mediator of inflammation is the transcription-factor NF-κB/RelA:p50. SEF (also known as IL-17RD) is a feedback antagonist of NF-κB/RelA:p50 that is emerging as an important link between inflammation and cancer.

The tumor suppressor Sef is a scaffold for the classical NF-κB/RELA:P50 signaling module.

The classical NF-κB transcription factor (RelA:p50) and the tumor suppressor Sef axis constitute a negative regulatory loop in which Sef, a target of NF-κB/RelA:p50, fine-tunes NF-κB/RelA:p50 transcriptional-activation in response to inflammatory stimuli trough binding to p50. Similar to the inhibitor IκBα, Sef sequesters NF-κB/RelA:p50 in the cytoplasm of unstimulated cells. Despite its key roles in regulating multiple cellular processes and its potential role as mediator between inflammation and cancer, Sef structural domains required to fulfill its tasks are poorly characterized, and how Sef specificity towards RelA:p50 is achieved is unknown.

Expression and regulation of the tumor suppressor, SEF, during folliculogenesis in humans and mice.

Similar expression to FGF (Sef or IL17-RD), is a tumor suppressor and an inhibitor of growth factors as well as of pro-inflammatory cytokine signaling. In this study, we examined the regulation of Sef expression by gonadotropins during ovarian folliculogenesis. In sexually immature mice, in situ hybridization (ISH) localized Sef gene expression to early developing oocytes and granulosa cells (GC) but not to theca cells.

Mechanisms of activation of the paternally expressed genes by the Prader-Willi imprinting center in the Prader-Willi/Angelman syndromes domains.

The Prader-Willi syndrome/Angelman syndrome (PWS/AS) imprinted domain is regulated by a bipartite imprinting control center (IC) composed of a sequence around the SNRPN promoter (PWS-IC) and a 880-bp sequence located 35 kb upstream (AS-IC). The AS-IC imprint is established during gametogenesis and confers repression upon PWS-IC on the maternal allele. Mutation at PWS-IC on the paternal allele leads to gene silencing across the entire PWS/AS domain.