國家衛生研究院 NHRI:Item 3990099045/7525

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Periodical Articles > Item 3990099045/7525

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Title:	Zinc-dependent interaction between JAB1 and pre-S2 mutant large surface antigen of hepatitis B virus and its implication for viral hepatocarcinogenesis
Authors:	Hsu, JL;Chuang, WJ;Su, IJ;Gui, WJ;Chang, YY;Lee, YP;Ai, YL;Chuang, DT;Huang, W
Contributors:	Division of Infectious Diseases
Abstract:	Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. The pre-S2 mutant large HBV surface (Delta2 LHBS) protein, which contains an in-frame deletion of approximately 17 amino acids in LHBS, is highly associated with risks and prognoses of HBV-induced HCC. It was previously reported that Delta2 LHBS interacts with the Jun activation domain-binding protein 1 (JAB1), a zinc metalloprotease. This promotes the degradation of the cell cycle regulator p27Kip1, and is believed to be the major mechanism for Delta2 LHBS-induced HCC. In this study it was found that the interaction between JAB1 and Delta2 LHBS is facilitated by divalent metal Zn2+ ions. The binding of JAB1 to Delta2 LHBS requires the JAB1/CSN5 MPN metalloenzyme (JAMM) motif and residue H138 that binds to Zn2+ ions in JAB1. Isothermal titration calorimetry showed that Delta2 LHBS binds directly to Zn2+ ions in a two-site binding mode. Residues H71 and H116 in Delta2 LHBS, which also contact Zn2+ ions, are too indispensable for Delta2 LHBS-mediated p27Kip1 degradation in human HuH7 cells. These results suggest that developing drugs that interrupt interactions between Delta2 LHBS and JAB1 can be potentially used to mitigate Delta2 LHBS-associated risks for HCC.
Date:	2013-12
Relation:	Journal of Virology. 2013 Dec;87(23):12675-12684.
Link to:	http://dx.doi.org/10.1128/jvi.01497-13
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-538X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000327183800017
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84887208273
Appears in Collections:	[Ih-Jen Su(2002-2015)] Periodical Articles

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