Interaction of hepatitis B virus X protein with a serine protease, tryptase TL2 as an inhibitor.
X protein of hepatitis B virus (HBV) transactivates transcription of various viral and cellular genes. It has been suggested that X protein plays a major role in hepatocarcinogenesis by HBV. The protein possesses amino acid sequence homology to the functionally essential domain of Kunitz-type serine protease inhibitors. This Kunitz domain-like sequence in X protein is indispensable for the transactivation function. To clarify whether X protein has a serine protease inhibitor activity, a search was made for serine proteases which interact with, but not degrade X protein. Tryptase TL2, one of serine proteases in hepatic cells, was found to directly interact with X protein without degradation. Moreover, the activities of tryptase TL2 and an analogous protease were substantially inhibited by X protein. These results suggest that transactivation function of X protein is exerted by modulation of the hepatic serine protease activity, giving rise to quantitative or qualitative change of cellular transcription factor(s) through protection from proteolytic degradation and/or suppression of processing.
Takada
S
S
Department of Gene Research, Cancer Institute, JFCR, Tokyo, Japan.
Kido
H
H
Fukutomi
A
A
Mori
T
T
Koike
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology; D053802:Tryptases; D054334:Viral Regulatory and Accessory Proteins
D015699:HIV Envelope Protein gp120; D015842:Serine Proteinase Inhibitors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D012697:Serine Endopeptidases; D053802:Tryptases; C070201:tryptase TL(2)