Physical interaction between hepatitis C virus NS4B protein and CREB-RP/ATF6beta.
By using a yeast two-hybrid assay, cyclic AMP-response-element-binding protein-related protein (CREB-RP), also called activating transcription factor 6beta (ATF6beta), was identified as a cellular protein that interacts with the NS4B protein of hepatitis C virus. An N-terminal half of NS4B and a central portion of CREB-RP/ATF6beta containing the basic leucine zipper (bZIP) domain were involved in the interaction. The interaction between NS4B and CREB-RP/ATF6beta was demonstrated also in mammalian cells by co-immunoprecipitation and confocal microscopic analyses using specific antibodies. The bZIP domain of ATF6alpha, which shares high sequence similarity with CREB-RP/ATF6beta, was also shown to interact with NS4B in yeast although the interaction was weaker than that between NS4B and CREB-RP/ATF6beta. CREB-RP/ATF6beta and ATF6alpha are known as endoplasmic reticulum (ER) stress-induced transcription factors. Collectively, our results imply the possibility that NS4B modulates certain cellular responses upon ER stress through the physical interaction with CREB-RP/ATF6beta and ATF6alpha.
Tong
Wen Yan
WY
Division of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan.
Nagano-Fujii
Motoko
M
Hidajat
Rachmat
R
Deng
Lin
L
Takigawa
Yuki
Y
Hotta
Hak
H
D051702:Activating Transcription Factor 6; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers; D046911:Macromolecular Substances; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; C093542:NS4 protein, hepatitis C virus; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins