Pom121 and Npipa genes function in cell death at the nuclear envelope.

We demonstrate here interplay between the nuclear envelope and cell death dynamics involving Pom121 family nuclear pore complex genes. We surmised Pom121 controlled cell death in normal and cancer cells. Consistent with this hypothesis, depletion of Pom121 altered mitochondrial cell death signaling manifested by activation of MFF. Nutrient signaling was affected by Pom121 depletion in prostate cancer cells with concomitant activation of SESN3 and DEPTOR. We demonstrate a relationship between transcriptional activity in the nucleolus and Pom121 involving Nolc1, Ncl and Nol6. Pom121 depletion activated p53 target gene Tp53tg1. Depletion of Pom121 in cancer cells was associated with other aspects of cell death program engagement including loss of LDHA and LDHB. We demonstrate here control of the Pdcd family by Pom121: Pom121 depletion resulted in loss of Pdcd2 and Pdcd11 but activation of Pdcd4.