HSC90 is required for nascent hepatitis C virus core protein stability in yeast cells.
Hepatitis C virus core protein (Core) contributes to HCV pathogenicity. Here, we demonstrate that Core impairs growth in budding yeast. We identify HSP90 inhibitors as compounds that reduce intracellular Core protein level and restore yeast growth. Our results suggest that HSC90 (Hsc82) may function in the protection of the nascent Core polypeptide against degradation in yeast and the C-terminal region of Core corresponding to the organelle-interaction domain was responsible for Hsc82-dependent stability. The yeast system may be utilized to select compounds that can direct the C-terminal region to reduce the stability of Core protein.
Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Naoko
N
Kubota
Yasutaka
Y
Inayoshi
Naoko
N
Satoh
Takashi
T
Fukuda
Kenta
K
Iwai
Hiroshi
H
Tomoda
Michinori
M
Kohara
Kazuhiro
K
Kataoka
Akira
A
Shimamoto
Yasuhiro
Y
Furuichi
Akio
A
Nomoto
Akira
A
Naganuma
Shusuke
S
Kuge
D045744:Cell Line, Tumor / Q000821:virology; D005656:Fungal Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000821:virology*; D013997:Time Factors; D014758:Viral Core Proteins / Q000378:metabolism*
D005656:Fungal Proteins; D010455:Peptides; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D049452:Green Fluorescent Proteins