The endoplasmic reticulum stress-inducible protein Niban regulates eIF2α and S6K1/4E-BP1 phosphorylation

The Ariban/NIBAN gene is specifically expressed in hereditary renal carcinomas of model animals and in human malignancies, including renal cancers. Although the expression profiles of Nihan/NIBAN suggest that it plays an important role in carcinogenesis, no functional information has yet been reported. In this study, we found that the levels of Niban/NIBAN mRNA and protein were induced by treatment with tunicamycin, an inducer of endoplasmic reticulum (ER) stress. To elucidate Niban's in vivo function, we generated a Niban knockout mouse. Niban(-/-) mouse showed no obvious phenotype. Unexpectedly, we found that eukaryotic translational initiation factor (eIF) 2 alpha phosphorylation, which is up-regulated during ER stress, was increased in Niban(-/-) cells relative to wild-type control cells. In addition, decreased phosphorylation of p70 ribosomal S6 subunit kinase (S6K) 1 and eukaryotic initiation factor 4E-binding protein (4E-BP) 1 was also detected in Niban(-/-) cells. Similar effects were observed following transfection of NIBAN-specific interfering RNAs in HeLa cells. Thus, Niban positively affects protein translation machineries. Additionally, suppression of NIBAN expression in HeLa cells promoted apoptosis. Together these results suggest that Niban is involved in the ER stress response, and that Niban can modulate cell death signaling by regulating translation. (c) 2007 Elsevier Inc. All rights reserved.