The endoplasmic reticulum stress-inducible protein Niban regulates eIF2alpha and S6K1/4E-BP1 phosphorylation.
The Niban/NIBAN gene is specifically expressed in hereditary renal carcinomas of model animals and in human malignancies, including renal cancers. Although the expression profiles of Niban/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) 2alpha 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.
Sun
Guo Dong
GD
Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Tokyo 113-8421, Japan.
Kobayashi
Toshiyuki
T
Abe
Masaaki
M
Tada
Norihiro
N
Adachi
Hiroyuki
H
Shiota
Akira
A
Totsuka
Yoshikazu
Y
Hino
Okio
O
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins
D014408:Biomarkers, Tumor; D015852:Eukaryotic Initiation Factor-2; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C105304:DLX4 protein, human; C516108:NIBAN1 protein, human; D051017:Apoptosis Regulatory Proteins; C495327:POLDIP3 protein, human; C492453:eukaryotic initiation factor-2 alpha, Toxoplasma gondii