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

Abstract

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.

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

“…However, there are several reports that support the ability of p50/p50 homodimers to activate transcription (Dechend et al, 1999;Kurland et al, 2001;Priel et al, 2005). On the basis of our experiments with antisense oligonucleotides against p65 and p50, it is possible that p65/p50 heterodimers may also bind to a yet to be identified site of the let-7a-3/let7-cluster and activate its transcription.…”

Activation of the NF-κB pathway by the leukemogenic TEL-Jak2 and TEL-Abl fusion proteins leads to the accumulation of antiapoptotic IAP proteins and involves IKKα

“…Phosphorylated serine536-p65/RelA species were also detected in the three cell lines; such phosphorylation of the p65 subunit has been reported in hematopoietic cells upon cytokine or LTb induction (Hayden and Ghosh, 2004) and as the consequence of the viral protein Tax-mediated cellular transformation (O'Mahony et al, 2004). The IkB-related B-cell leukemia/lymphoma 3 (Bcl-3) was found in nuclear extracts as repeatedly reported in lymphoid cells, where it is known to participate to the induction of NF-kBtarget genes in association with p50 and p52 (Dechend et al, 1999). Finally, enhanced protein levels of IkBa (but not IkBb and IkBe) and of phospho-ser32/36-IkBa were detected in nuclear and cytoplasmic fractions of the two oncogene-expressing cells when compared to parental cells (Figure 2a).…”

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

“…5 These data suggest that BCL-3 is an adaptor protein between NK-kB p50/p52 and other transcriptional regulators. 5 The t (14;19) or bcl-3 gene rearrangement has been reported rarely in non-Hodgkin lymphomas, in approximately 35 cases, mostly in cases of chronic lymphocytic leukemia/small lymphocytic lymphoma, and less frequently in cases designated as follicular lymphoma, diffuse large B-cell lymphoma, Burkitt-like lymphoma, and one case of acute biphenotypic leukemia. [6][7][8][9][10][11][12] Although the t(14;19) is rare, BCL-3 expression has been shown in a few types of non-Hodgkin lymphoma not known to carry the t (14;19).…”