Protein phosphorylation as a key mechanism for the regulation of BCL-3 activity

[en] Constitutive NF-kappaB activation, a hallmark of many human cancers, upregulates anti-apoptotic gene expression and therefore disrupts the balance between apoptosis and proliferation. In some lymphomas, this constitutive NF-kappaB activity is the result of point mutations or translocations of the genes coding for NF-kappaB inhibitors, namely IkappaBalpha or p100. The BCL-3 protein is another member of the IkappaB family and is overexpressed in a subset of human B-cell chronic lymphocytic leukemias because of a chromosomal translocation. This oncoprotein is phosphorylated by multiple kinases including GSK3 and this phosphorylation regulates BCL-3 function by modulating its oncogenic potential and by regulating the expression of a subset of its target genes. Therefore, deciphering the NF-kappaB/IkappaB protein phosphorylations is critical in order to better understand the molecular mechanisms of NF-kappaB-mediated oncogenesis.

Research center :

Giga-Signal Transduction - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Viatour, Patrick ; Université de Liège - ULiège > Chimie médicale

Merville, Marie-Paule ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine

Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Language :

English

Title :

Protein phosphorylation as a key mechanism for the regulation of BCL-3 activity

Publication date :

December 2004

Journal title :

Cell Cycle

ISSN :

1538-4101

eISSN :

1551-4005

Publisher :

Landes Bioscience

Volume :

Issue :

Pages :

1498-1501

Peer reviewed :

Peer Reviewed verified by ORBi

Name of the research project :

Insight into the oncogenic potential of BCL-3

Funders :

FNRS, TELEVIE, FBC, ARC ULG

Available on ORBi :

since 26 November 2008

Statistics

Number of views

72 (1 by ULiège)

Number of downloads

252 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Hayden MS, Ghosh S. Signaling to NF-κB. Genes Dev 2004; 18:2195-224.
McKeithan TW, Rowley JD, Shows TB, Diaz MO. Cloning of the chromosome translocation breakpoint junction of the t(14;19) in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 1987; 84:9257-60.
Ohno H, Takimoto G, McKeithan TW. The candidate proto-oncogene BCL-3 is related to genes implicated in cell lineage determination and cell cycle control. Cell 1990; 60:991-9.
Nishikori M, Maesako Y, Ueda C, Kurata M, Uchiyama T, Ohno H. High-level expression of BCL-3 differentiates t(2,5)(p23;q35)-positive anaplastic large cell lymphoma from hodgkin disease. Blood 2003; 101:2789-96.
Thornburg NJ, Pathmanathan R, Raab-Traub N. Activation of nuclear factor-κB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma. Cancer Res 2003; 63:8293-301.
Cogswell PC, Guttridge DC, Funkhouser WK, Baldwin AS Jr. Selective activation of NF-κ B subunits in human breast cancer: Potential roles for NF-κ B2/p52 and for Bcl-3. Oncogene 2000; 19:1123-31.
Bours V, Franzos, G, Azarenko V, Park S, Kanno T, Brown Siebenlist U. The oncoprotein BCL-3 directly transactivates through κB motifs via association with DNA-binding p50B homodimers. Cell 1993; 72:729-39.
Fujita T, Nolan GP, Liou HC, Scott ML, Baltimore D. The candidate proto-oncogene BCL-3 encodes a transcriptional coactivator that activates through NF-κ B p50 homodimers. Genes Dev 1993; 7:1354-63.
Franzoso G, Bours V, Azarenko V, Park S, Tomita-Yamaguchi M, Kanno T, Brown K Siebenlist U. The oncoprotein BCL-3 can facilitate NF-κ B-mediated transactivation by removing inhibiting p50 homodimers from select κ B sites. EMBO J 1993; 12:3893-901.
Grundström S, Anderson P, Scheipers P, Sundstedt A. Bcl-3 and NFκB p50-p50 homodimers act as transcriptional repressors in tolerant CD4+ T cells. J Biol Chem 2004; 279:8460-8.
Kuwata H, Watanabe Y, Miyoshi H, Yamamoto M, Kaisho T, Takeda K, Akira S. IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-α production in macrophages. Blood 2003; 102:4123-9.
Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG, Scheidereit C, Leutz A. The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear coregulators. Oncogene 1999; 18:3315-23.
Wessells J, Baer M, Young HA, Claudio E, Brown K, Siebenlist U, Johnson P. BCL-3 and NF-κB p50 attenuate LPS-induced inflammatory responses in macrophages. J Biol Chem in press.
Viatour P Dejardin E Warnier M, Lair F, Claudio E, Bureau F, Marine JC, Merville MP, Maurer U, Green D, Piette J, Siebenlist U, Bours V, Chariot A. GSK3-Mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity. Mol Cell 2004; 16:35-45.
Leung TH, Hoffman A, Baltimore D. One nucleotide in a κB site can determine cofactor specificity for NF-κB dimers. Cell 2004; 118:453-64.
Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG. Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-κB and β-amyloid precursor protein. Cell 2002; 110:55-67.
Devoogdt N, Hassanzadeh Ghassabeh G, Zhang J, Brys L, De Baetselier P, Revets H. Secretory leukocyte protease inhibitor promotes the tumorigenic and metastatic potential of cancer cells. Proc Natl Acad Sci USA 2003; 100:5778-82.
Bundy DL, McKeithan TW. Diverse effects of BCL3 phosphorylation on its modulation of NF-κB p52 homodimer binding to DNA. J Biol Chem 1997; 272:33132-9.
Nolan GP, Fujita T, Bhatia K, Huppi C, Liou H-C, Scott ML, Baltimore D. The BCL-3 proto-oncogene encodes a nuclear IκB-like molecule that preferentially interacts with NF-κB p50 and p52 in a phosphorylation- dependent manner. Mol Cell Biol 1993; 13:3557-66.
Franzoso G, Carlson L, Scharton-Kersten T, Shores EW, Epstein S, Grinberg A, Tran T, Shacter E, Leonardi A, Anver M, Love P, Sher A, Siebenlist U. Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions. Immunity 1997; 6:479-90.
Franzoso G, Carlson L, Poljak L, Shores EW, Epstein S, Leonardi A, Grinberg A, Tran T, Scharton-Kersten T, Anver M, Love P, Brown K, Siebenlist U. Mice deficient in nuclear factor (NF)-κB/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture. J Exp Med 1998; 187:147-59.
Caamano JH, Perez P, Lira SA, Bravo R. Constitutive expression of Bcl-3 in thymocytes increases the DNA binding of NF-κB1 (p50) homodimers in vivo. Mol Cell Biol 1996; 16:1342-8.
Westerheide SD, Mayo MW, Anest V, Hanson JL, Baldwin Jr AS. The putative oncoprotein Bcl-3 induces cyclin D1 to stimulate G(1) transition. Mol Cell Biol 2001; 21:8428-36.
Poljak L, Carlson L, Cunningham K, Kosco-Vilbois MH, Siebenlist U. Distinct activities of p52/NF-κ B required for proper secondary lymphoid organ microarchitecture: Functions enhanced by Bcl-3. J Immunol 1999; 163:6581-8.
Conaway RC, Brower CS, Conaway JW. Emerging roles of ubiquitin in transcription regulation. Science 2002; 296:1254-8.
Freiman RN, Tjian R. Regulating the regulators: Lysine modifications make their mark. Cell 2003; 112:11-7.