Takada S, Kido H, Fukutomi A, Mori T, Koike K
Department of Gene Research, Cancer Institute, JFCR, Tokyo, Japan.
Oncogene. 1994 Feb;9(2):341-8.
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.
乙型肝炎病毒（HBV）的X蛋白可反式激活多种病毒和细胞基因的转录。有人提出，X蛋白在HBV引发的肝癌发生过程中起主要作用。该蛋白与Kunitz型丝氨酸蛋白酶抑制剂的功能必需结构域具有氨基酸序列同源性。X蛋白中这种类似Kunitz结构域的序列对于反式激活功能是必不可少的。为了阐明X蛋白是否具有丝氨酸蛋白酶抑制剂活性，人们寻找了与X蛋白相互作用但不降解它的丝氨酸蛋白酶。发现肝细胞中的丝氨酸蛋白酶之一类胰蛋白酶TL2可直接与X蛋白相互作用而不发生降解。此外，X蛋白可显著抑制类胰蛋白酶TL2和一种类似蛋白酶的活性。这些结果表明，X蛋白的反式激活功能是通过调节肝脏丝氨酸蛋白酶活性来实现的，通过防止蛋白水解降解和/或抑制加工过程，导致细胞转录因子发生定量或定性变化。
