Home LiteratureArticle Details
PMID: 16344472 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Up-regulation of beta-catenin by a viral oncogene correlates with inhibition of the seven in absentia homolog 1 in B lymphoma cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 51 ·2005-12-20 ·Pages 18431-6

Jang KL, Shackelford J, Seo SY, Pagano JS

Abstract

The protein levels of beta-catenin are tightly regulated by the ubiquitin/proteasome system. We provide evidence that two distinct ubiquitin-dependent degradation pathways for beta-catenin are active in the same Burkitt's lymphoma cells: Along with the classical glycogen-synthase kinase 3beta-dependent destruction machinery, degradation of beta-catenin through seven in absentia homolog 1 (Siah-1) ubiquitin ligase is functional in these cells. We show that inhibition of endogenous Siah-1 stabilizes and activates beta-catenin in B cells. The principal Epstein-Barr virus oncoprotein, latent membrane protein 1, is involved in beta-catenin up-regulation, and expression of latent membrane protein 1 in B lymphoma cells is associated with decreased Siah-1 RNA and protein levels. Thus, we demonstrate the significance of the endogenous Siah-1-dependent ubiquitin/proteasome pathway for beta-catenin degradation in malignant human cells and its regulation by a viral oncogene.

MeSH Terms
Cell Line Glycogen Synthase Kinase 3/metabolism Glycogen Synthase Kinase 3 beta Lymphoma, B-Cell/genetics,metabolism,pathology Nuclear Proteins/antagonists & inhibitors,genetics,metabolism Oncogene Proteins, Viral/genetics,metabolism Protein Binding Ubiquitin/metabolism Ubiquitin-Protein Ligases/antagonists & inhibitors,genetics,metabolism Up-Regulation Viral Matrix Proteins/genetics,metabolism beta Catenin/metabolism
Chemicals
EBV-associated membrane antigen, Epstein-Barr virus Nuclear Proteins Oncogene Proteins, Viral Ubiquitin Viral Matrix Proteins beta Catenin Ubiquitin-Protein Ligases seven in absentia proteins GSK3B protein, human Glycogen Synthase Kinase 3 beta Glycogen Synthase Kinase 3
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jang Kyung Lib
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
Shackelford Julia
Seo So Young
Pagano Joseph S
References (35)
35 references, click to expand
  1. Epstein-Barr virus activates beta-catenin in type III latently infected B lymphocyte lines: association with deubiquitinating enzymes.
    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15572-6 PMID: 14663138
  2. The ubiquitin system: pathogenesis of human diseases and drug targeting.
    Biochim Biophys Acta. 2004 Nov 29;1695(1-3):3-17 PMID: 15571805
  3. Convergence of Wnt, beta-catenin, and cadherin pathways.
    Science. 2004 Mar 5;303(5663):1483-7 PMID: 15001769
  4. Siah-1b is a direct transcriptional target of p53: identification of the functional p53 responsive element in the siah-1b promoter.
    Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3510-5 PMID: 14985507
  5. N-terminal ubiquitination: more protein substrates join in.
    Trends Cell Biol. 2004 Mar;14(3):103-6 PMID: 15055197
  6. Wnt-independent beta-catenin transactivation in tumor development.
    Cell Cycle. 2004 May;3(5):571-3 PMID: 15107603
  7. Tumor viruses and cell signaling pathways: deubiquitination versus ubiquitination.
    Mol Cell Biol. 2004 Jun;24(12):5089-93 PMID: 15169876
  8. Peroxisome proliferator-activated receptor gamma activation can regulate beta-catenin levels via a proteasome-mediated and adenomatous polyposis coli-independent pathway.
    J Biol Chem. 2004 Aug 20;279(34):35583-94 PMID: 15190077
  9. Accumulation of cytoplasmic beta-catenin and nuclear glycogen synthase kinase 3beta in Epstein-Barr virus-infected cells.
    J Virol. 2004 Nov;78(21):11648-55 PMID: 15479806
  10. Infectious agents and cancer: criteria for a causal relation.
    Semin Cancer Biol. 2004 Dec;14(6):453-71 PMID: 15489139
  11. Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes.
    J Cell Biol. 2004 Oct 25;167(2):339-49 PMID: 15492040
  12. Roles of the ITAM and PY motifs of Epstein-Barr virus latent membrane protein 2A in the inhibition of epithelial cell differentiation and activation of {beta}-catenin signaling.
    J Virol. 2005 Feb;79(4):2375-82 PMID: 15681438
  13. Regulation of beta-catenin signaling in the Wnt pathway.
    Biochem Biophys Res Commun. 2000 Feb 16;268(2):243-8 PMID: 10679188
  14. Nuclear beta-catenin displays GSK-3beta- and APC-independent proteasome sensitivity in melanoma cells.
    Biochim Biophys Acta. 2000 Feb 28;1495(3):308-18 PMID: 10699468
  15. Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus.
    Science. 2000 Mar 3;287(5458):1606-9 PMID: 10733430
  16. Wnt signaling and cancer.
    Genes Dev. 2000 Aug 1;14(15):1837-51 PMID: 10921899
  17. Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses.
    Mol Cell. 2001 May;7(5):915-26 PMID: 11389839
  18. Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein.
    Mol Cell. 2001 May;7(5):927-36 PMID: 11389840
  19. Adhesion signaling: how beta-catenin interacts with its partners.
    Curr Biol. 2001 Oct 2;11(19):R792-4 PMID: 11591340
  20. Intracellular signaling molecules activated by Epstein-Barr virus for induction of interferon regulatory factor 7.
    J Virol. 2001 Dec;75(24):12393-401 PMID: 11711629
  21. Wnt signaling controls the phosphorylation status of beta-catenin.
    J Biol Chem. 2002 May 17;277(20):17901-5 PMID: 11834740
  22. Casein kinase 1: a Wnt'er of disconnect.
    Curr Biol. 2002 Jul 23;12(14):R499-R501 PMID: 12176352
  23. P53 mutation as a source of aberrant beta-catenin accumulation in cancer cells.
    Oncogene. 2002 Nov 14;21(52):7971-80 PMID: 12439747
  24. A binding motif for Siah ubiquitin ligase.
    Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3101-6 PMID: 12626763
  25. The ubiquitin proteolytic system and pathogenesis of human diseases: a novel platform for mechanism-based drug targeting.
    Biochem Soc Trans. 2003 Apr;31(2):474-81 PMID: 12653666
  26. Adenomatous polyposis coli (APC)-independent regulation of beta-catenin degradation via a retinoid X receptor-mediated pathway.
    J Biol Chem. 2003 Aug 8;278(32):29954-62 PMID: 12771132
  27. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation.
    J Cell Biol. 2003 Sep 1;162(5):899-908 PMID: 12952940
  28. Epstein-Barr virus latent membrane protein 2A activates beta-catenin signaling in epithelial cells.
    J Virol. 2003 Nov;77(22):12276-84 PMID: 14581564
  29. Establishment in continuous culture of a new type of lymphocyte from a "Burkitt like" malignant lymphoma (line D.G.-75).
    Int J Cancer. 1977 Jan;19(1):27-33 PMID: 188769
  30. Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells.
    Proc Natl Acad Sci U S A. 1987 Nov;84(22):8060-4 PMID: 2825176
  31. Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box.
    EMBO J. 1991 Jan;10(1):123-32 PMID: 1989880
  32. Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins.
    Mol Cell Biol. 1999 Jan;19(1):724-32 PMID: 9858595
  33. Inactivating mutations of the Siah-1 gene in gastric cancer.
    Oncogene. 2004 Nov 11;23(53):8591-6 PMID: 15467739
  34. Pharmacological inhibitors of glycogen synthase kinase 3.
    Trends Pharmacol Sci. 2004 Sep;25(9):471-80 PMID: 15559249
  35. The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome.
    J Biol Chem. 2004 Feb 13;279(7):5374-9 PMID: 14645235
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0504054102
Published
2005-12-20
Epub
2005-00-12
Pages
18431-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1317901
Subset
IM
Grants
NCI NIH HHS · P01 CA019014 · United States
NCI NIH HHS · CA 19014 · United States
External Links
PubMed source DOI: 10.1073/pnas.0504054102 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2