Bcl-3 Expression Promotes Cell Survival following Interleukin-4 Deprivation and Is Controlled by AP1 and AP1-Like Transcription Factors

Rebollo, Angelita; Dumoutier, Laure; Renauld, Jean‐Christophe; Zaballos, Ángel; Ayllón, Verónica; Martı́nez-A, Carlos

doi:10.1128/mcb.20.10.3407-3416.2000

Cited by 99 publications

(78 citation statements)

References 47 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent findings have correlated BCL3 expression with increased cellular proliferation and survival in lymphocytes (Ong et al, 1998;Rebollo et al, 2000;Mitchell et al, 2001). Thus, we speculated that upregulation of BCL3 could contribute to the IL-6-mediated antiapoptotic effect in MM cells.…”

Section: Discussionmentioning

confidence: 90%

“…It is itself an NF-kB target gene whose expression is induced by a number of classic NF-kB-inducing stimuli such as tumor necrosis factor-a (TNF-a) (Brasier et al, 2001) or IL-1 (Elliott et al, 2002). Although IL-4 promotes BCL3 transcription in T cells through an AP-1-dependent mechanism (Rebollo et al, 2000), IL-9 was reported to induce BCL3 expression through the Jak/Stat pathway (Richard et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Sequence analysis of the BCL3 gene locus revealed four potential Stat binding sites within the evolutionarily conserved regions described previously. In addition to cis-regulatory elements of the BCL3 promoter (Rebollo et al, 2000;Brasier et al, 2001), two downstream enhancers within intron 2 (named HS3 and HS4) have been identified by phylogenetic footprint analysis and DNase hypersensitivity assays (Ge et al, 2003). One of the Stat motifs is located within HS3 and three within HS4 (Figure 2a).…”

Section: Il-6 Initiates Stat3 Binding To Intronic Enhancers Of the Bcmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Il-6 Initiates Stat3 Binding To Intronic Enhancers Of the Bcmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…bcl-3 gene expression is induced by many cell growth-or survival-promoting factors in lymphoid cell lines, suggesting that BCL-3 is involved in cell proliferation and survival. 19 In one study, transgenic mice expressing BCL-3 were found to have an expansion of B-cells in vivo, 20 further suggesting a role for BCL-3 in cell proliferation or survival. On the other hand, BCL-3-deficient mice are susceptible to certain Table 2 …”

Section: Bcl-3 In Lymphomas O Canoz Et Al Cells With Various Inducersmentioning

confidence: 99%

“…BCL-3 expression in interleukin 4-deprived T cells protects these cells from apoptosis. 19 In anaplastic large-cell lymphoma, a prior study has shown that BCL-3 expression and both genetic and epigenetic modifications of the bcl-3 gene may be associated with oncogenesis. 13 Izban and colleagues 30 have reported that NF-kB p65 is expressed in cutaneous T-cell lymphoma cell lines and neoplastic T lymphocytes from patient samples of mycosis fungoides, and they also showed that nuclear NF-kB activity is required for cell survival and resistance to apoptosis in the neoplastic cells.…”

Section: Bcl-3 In Lymphomasmentioning

confidence: 99%

Immunohistochemical detection of BCL-3 in lymphoid neoplasms: a survey of 353 cases

et al. 2004

View full text Add to dashboard Cite

The bcl-3 gene at chromosome 19q13 encodes a member of the IjB family involved in regulating the NFjB pathway. Originally identified by its involvement in the rare t(14:19)(q32;q13), BCL-3 expression has never been analyzed in a wide variety of lymphomas. We assessed BCL-3 expression in 353 cases of non-Hodgkin lymphoma and Hodgkin lymphoma using formalin-fixed, paraffin-embedded tissue specimens, a monoclonal antibody specific for BCL-3, and immunohistochemical methods. Of 172 B-cell lymphomas, 10 (6%) were positive for BCL-3, including six of 23 (26%) diffuse large B-cell lymphoma, one of 17 (6%) small lymphocytic lymphoma, one of 26 (4%) follicular lymphoma, and two of 49 (4%) mantle cell lymphoma. All other B-cell neoplasms were negative, including marginal zone lymphoma (n ¼ 24, 11 extranodal, nine nodal, four splenic), Burkitt lymphoma (n ¼ 10), lymphoplasmacytic lymphoma (n ¼ 10), lymphoblastic lymphoma (n ¼ 8), and plasmacytoma (n ¼ 5). Of 111 T/NK-cell lymphomas, 25 (23%) were positive for BCL-3, including 13 of 40 (32%) anaplastic large-cell lymphoma, three of 10 (30%) angioimmunoblastic T-cell lymphoma, two of eight (25%) extranodal NK/T-cell lymphoma of nasal type, three of 12 (25%) mycosis fungoides, one of five (20%) enteropathy-type T-cell lymphoma, and two of 21 (10%) peripheral T-cell lymphoma unspecified. All other T-cell neoplasms were negative, including lymphoblastic lymphoma (n ¼ 6), prolymphocytic leukemia (n ¼ 6), and subcutaneous panniculitis-like T-cell lymphoma (n ¼ 3). Of 70 Hodgkin lymphomas, of all types, 29 (41%) were positive for BCL-3. The relatively high frequency of BCL-3 expression in some non-Hodgkin and Hodgkin lymphoma types raises the possibility that BCL-3 is involved in the pathogenesis of these tumors, and may be a target of new therapies.

show abstract

BCL3

McKeithan¹

2002

Wiley Encyclopedia of Molecular Medicine

View full text Add to dashboard Cite

Bcl-3 Expression Promotes Cell Survival following Interleukin-4 Deprivation and Is Controlled by AP1 and AP1-Like Transcription Factors

Cited by 99 publications

References 47 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

Immunohistochemical detection of BCL-3 in lymphoid neoplasms: a survey of 353 cases

BCL3

Contact Info

Product

Resources

About