The X protein of hepatitis B virus binds to the F box protein Skp2 and inhibits the ubiquitination and proteasomal degradation of c-Myc

被引：54

作者：

Kalra, N ^{[1
]}

Kumar, V ^{[1
]}

机构：

[1] Int Ctr Genet Engn & Biotechnol, Virol Grp, New Delhi 110067, India

来源：

FEBS LETTERS | 2006年 / 580卷 / 02期

关键词：

F box protein; X protein of hepatitis B virus; c-Myc; Skp1-cullin1-F box protein complex; Skp2; ubiquitination;

D O I：

10.1016/j.febslet.2005.12.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The HBx protein of hepatitis B virus is involved in deregulation of cell cycle and development of hepatocellular carcinoma. Since c-Myc also plays an important role in cell proliferation and tumor development, we studied its regulation by HBx in a human hepatoma cell line. Co-expression of HBx and c-Myc resulted in increased stability of intracellular c-Myc. HBx blocked the ubiquitination of Myc through a direct interaction with the F box region of Skp2 and destabilization of the SCFSkp2 Complex. We suggest that sustained presence of c-Myc combined with mitogenic activity inherent to HBx may be associated with cell cycle deregulation and transformation. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：431 / 436

页数：6

共 30 条

[1] FULL-LENGTH AND TRUNCATED VERSIONS OF THE HEPATITIS-B VIRUS (HBV) X-PROTEIN (PX) TRANSACTIVATE THE CMYC PROTOONCOGENE AT THE TRANSCRIPTIONAL LEVEL [J].

BALSANO, C ;

AVANTAGGIATI, ML ;

NATOLI, G ;

DEMARZIO, E ;

WILL, H ;

PERRICAUDET, M ;

LEVRERO, M .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 176 (03) :985-992

[2] Viruses and the 26S proteasome: hacking into destruction [J].

Banks, L ;

Pim, D ;

Thomas, M .

TRENDS IN BIOCHEMICAL SCIENCES, 2003, 28 (08) :452-459

[3] The human immunodeficiency virus type 1 Vpu protein inhibits NF-κB activation by interfering with βTrCP-mediated degradation of IκB [J].

Bour, S ;

Perrin, C ;

Akari, H ;

Strebel, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (19) :15920-15928

[4] The SCF ubiquitin ligase: Insights into a molecular machine [J].

Cardozo, T ;

Pagano, M .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (09) :739-751

[5] A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition [J].

Coscoy, L ;

Sanchez, DJ ;

Ganem, D .

JOURNAL OF CELL BIOLOGY, 2001, 155 (07) :1265-1273

[6] Transient excess of MYC activity can elicit genomic instability and tumorigenesis [J].

Felsher, DW ;

Bishop, JM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3940-3944

[7] The ubiquitin-proteasome proteolytic pathway: Destruction for the sake of construction [J].

Glickman, MH ;

Ciechanover, A .

PHYSIOLOGICAL REVIEWS, 2002, 82 (02) :373-428

[8] Skp2 is oncogenic and overexpressed in human cancers [J].

Gstaiger, M ;

Jordan, R ;

Lim, M ;

Catzavelos, C ;

Mestan, J ;

Slingerland, J ;

Krek, W .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (09) :5043-5048

[9] Rhabdoviruses and the cellular ubiquitin-proteasome system: a budding interaction [J].

Harty, RN ;

Brown, ME ;

McGettigan, JP ;

Wang, GL ;

Jayakar, HR ;

Huibregtse, JM ;

Whitt, MA ;

Schnell, MJ .

JOURNAL OF VIROLOGY, 2001, 75 (22) :10623-10629

[10] Hepatitis B virus X protein is both a substrate and a potential inhibitor of the proteasome complex [J].

Hu, ZY ;

Zhang, ZS ;

Doo, E ;

Coux, O ;

Goldberg, AL ;

Liang, TJ .

JOURNAL OF VIROLOGY, 1999, 73 (09) :7231-7240

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