The proto-oncogene bcl-3 encodes an I kappa B protein.

Kerr, Lawrence D.; Duckett, Colin S.; Wamsley, Penny; Zhang, Qiang; Chiao, Paul J.; Nabel, Gary J.; McKeithan, Timothy W.; Baeuerle, Patrick A.; Verma, Inder M.

doi:10.1101/gad.6.12a.2352

Cited by 120 publications

(93 citation statements)

References 18 publications

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“…BCL3 can either stimulate or inhibit NF-kB-dependent transcription (Kerr et al, 1992;Wulczyn et al, 1992;Franzoso et al, 1993;Fujita et al, 1993;Kuwata et al, 2003). Consistent with the observation that many transcription factors are auto-regulated (Angel et al, 1988;Chen et al, 1995), our data demonstrate that BCL3 negatively regulates its own transcription.…”

Section: Discussionsupporting

confidence: 91%

“…BCL3 is mainly located in the nucleus and regulates NF-kB transcriptional activity Nolan et al, 1993). By forming complexes with p50 and p52 homodimers, it can either activate Fujita et al, 1993) or repress (Kerr et al, 1992;Wulczyn et al, 1992;Kuwata et al, 2003) gene transcription. Furthermore, phosphorylation plays an important role in regulating the transcriptional function of BCL3 Bundy and McKeithan, 1997).…”

Section: Introductionmentioning

confidence: 99%

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BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription

Brocke-Heidrich

Cvijic

et al. 2006

Oncogene

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BCL3 is a proto-oncogene affected by chromosomal translocations in some patients with chronic lymphocytic leukemia. It is an IjB family protein that is involved in transcriptional regulation of a number of NF-jB target genes. In this study, interleukin (IL)-6-induced BCL3 expression and its effect on survival of multiple myeloma (MM) cells were examined. We demonstrate the upregulation of BCL3 by IL-6 in INA-6 and other MM cell lines. Sequence analysis of the BCL3 gene locus revealed four potential signal transducer and activator of transcription (Stat) binding sites within two conserved intronic enhancers regions: one located within enhancer HS3 and three within HS4. Chromatin immunoprecipitation experiments showed increased Stat3 binding to both enhancers upon IL-6 stimulation. Silencing Stat3 expression by small interfering RNA (siRNA) abrogated BCL3 expression by IL-6. Using reporter gene assays, we demonstrate that BCL3 transcription depends on HS4. Mutation of the Stat motifs within HS4 abolished IL-6-dependent BCL3 induction. Furthermore, BCL3 transcription was inhibited by its own gene product. This repressive feedback is mediated by NF-jB sites within the promoter and HS3. Finally, we show that overexpression of BCL3 increases apoptosis, whereas BCL3-specific siRNA does not affect the viability of INA-6 cells suggesting that BCL3 is not essential for the survival of these cells.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription

Brocke-Heidrich

Cvijic

et al. 2006

Oncogene

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“…IkBa, IkBb and IkBe strongly prefer dimers containing RelA or c-Rel. In contrast, Bcl-3 has a strong preference towards p50 or p52 homodimers (Franzoso et al, 1992;Hatada et al, 1992;Kerr et al, 1992;Nolan et al, 1993;.…”

Section: Introductionmentioning

confidence: 96%

The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators

et al. 1999

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The proto-oncoprotein Bcl-3 is a member of the IkB family and is present predominantly in the nucleus. To gain insight into speci®c nuclear functions of Bcl-3 we have isolated proteins that interact with its ankyrin repeat domain. Using the yeast two-hybrid-system we identi®ed four novel binding partners of Bcl-3 in addition to NF-kB p50 and p52, previously known to associate with Bcl-3. The novel Bcl-3 interactors Jab1, Pirin, Tip60 and Bard1 are nuclear proteins which also bind to other transcription factors including c-Jun, nuclear factor I (NFI), HIV-1 Tat or the tumor suppressor and Polll holoenzyme component Brca1, respectively. Bcl-3, p50, and either Bard1, Tip60 or Pirin are sequestered into quarternary complexes on NF-kB DNA binding sites, whereas Jab1 enhances p50-Bcl-3-DNA complex formation. Furthermore, the histone acetylase Tip60 enhances Bcl-3-p50 activated transcription through an NF-kB binding site, indicating that quarternary complexes containing Bcl-3 interactors modulate NF-kB driven gene expression. These data implicate Bcl-3 as an adaptor between NF-kB p50/p52 and other transcription regulators and suggest that its gene activation function may at least in part be due to recruitment of the Tip60 histone actetylase.

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“…IkBb also interacts with the same heterodimers as IkBa but is degraded with slower kinetics and functions in the persistent activation of NF-kB (Ghosh et al, 1998). Bcl-3, a noninhibitory member of the IkB family (Ohno et al, 1990;Kerr et al, 1992) that is associated with certain leukemias and lymphomas (McKeithan et al, 1997), functions to stimulate transcription through interactions with the p50 or p52 NF-kB subunits (Bours et al, 1993;Fujita et al, 1993) and to increase nuclear levels of p50 homodimers (Zhang et al, 1994;Watanabe et al, 1997). Bcl-3-p50 complexes can be activated following inducible phosphorylation of the p105 precursor by the IkB kinase .…”

Section: Introductionmentioning

confidence: 99%

Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3

et al. 2000

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Members of the NF-kB/Rel transcription factor family have been shown recently to be required for cellular transformation by oncogenic Ras and by other oncoproteins and to suppress transformation-associated apoptosis. Furthermore, NF-kB has been shown to be activated by several oncoproteins including HER2/Neu, a receptor tyrosine kinase often expressed in human breast cancer. Human breast cancer cell lines, human breast tumors and normal adjacent tissue were analysed by gel mobility shift assay, immunoblotting of nuclear extracts and immunohistochemistry for activation of NF-kB. Furthermore, RNA levels for NF-kB-activated genes were analysed in order to determine if NF-kB is functionally active in human breast cancer. Our data indicate that the p65/RelA subunit of NF-kB is activated (i.e., nuclear) in breast cancer cell lines. However, breast tumors exhibit an absence or low level of nuclear p65/RelA but show activated c-Rel, p50 and p52 as compared to nontumorigenic adjacent tissue. Additionally, the IkB homolog Bcl-3, which functions to stimulate transcription with p50 or p52, was also activated in breast tumors. There was no apparent correlation between estrogen receptor status and levels of nuclear NF-kB complexes. Transcripts of NF-kB-regulated genes were found elevated in breast tumors, as compared to adjacent normal tissue, indicating functional NF-kB activity. These data suggest a potential role for a subset of NF-kB and IkB family proteins, particularly NF-kB/p52 and Bcl-3, in human breast cancer. Additionally, the activation of functional NF-kB in these tumors likely involves a signal transduction pathway distinct from that utilized by cytokines.

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The proto-oncogene bcl-3 encodes an I kappa B protein.

Cited by 120 publications

References 18 publications

BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription

BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription

The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators

Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3

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