URP2SF, a FERM and PH domain containing protein, regulates NF-kappaB and apoptosis

The transcription factor NF-kappaB plays an important role in inflammation and cell survival. Here, we report the functional characterization of URP2SF (UNC-112 related protein 2 short form), which is a novel protein containing FERM and PH domains. The protein is conserved in evolution across different species. Northern blot and RT-PCR analysis revealed that the expression of URP2SF appeared to be primarily confined to immune system. URP2SF protein localized to the whole cell. Over-expression of URP2SF strongly repressed NF-kappaB activity in the absence or presence of NF-kappaB stimulus. Importantly, URP2SF over-expression also induced cell apoptosis. Furthermore, suppression of URP2SF expression by small interference RNA significantly activated the NF-kappaB reporter gene activities, as well as attenuated TNF-alpha induced apoptosis. Therefore, our data show for the first time that URP2SF may act as a transcriptional repressor in NF-kappaB signaling pathway and regulate cell apoptotic pathway.