Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation.
Bcl3, an IkappaB protein, was originally isolated as a putative proto-oncogene in a subset of B cell chronic lymphocytic leukemias. Bcl3 was subsequently shown to associate tightly with and transactivate the NFkappaB p50 or p52 homodimer. Herein, we show that Bcl3 stimulates the activating protein-1 (AP-1) transactivation, either alone or in conjunction with transcription integrators steroid receptor coactivator-1 and CREB-binding protein/p300. The C-terminal 158 residues of Bcl3 exhibited an autonomous transactivation function and interacted with specific subregions of the AP-1 components c-Jun and c-Fos, CREB-binding protein/p300, and steroid receptor coactivator-1, as demonstrated by the yeast and mammalian two-hybrid tests as well as glutathione S-transferase pull-down assays. In addition, anti-HA antibody co-precipitated c-Jun from HeLa cells co-expressing c-Jun and HA-tagged Bcl3, consistent with the idea that Bcl3 directly associates with AP-1 in vivo. Furthermore, microinjection of Bcl3 expression vector into Rat-1 fibroblast cells significantly enhanced DNA synthesis and expression of c-jun, one of the cellular target genes of AP-1. These results suggest that Bcl3 may directly participate in the tumorigenesis processes as a novel transcription coactivator of the mitogenic transcription factor AP-1 in vivo.
Na
S Y
SY
Department of Biology, Chonnam National University, Kwangju 500-757, South Korea.
Choi
J E
JE
Kim
H J
HJ
Jhun
B H
BH
Lee
Y C
YC
Lee
J W
JW
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D004261:DNA Replication; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology*
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D020672:I-kappa B Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors