Abstract
BCL-6 gene alterations have been observed in 27 – 45% of diffuse large B-cell lymphomas (DLBs) with chromosomal translocations at 3q27. The deregulated expression of normal BCL-6 protein caused by this chromosomal translocation is believed to be responsible for lymphomagenesis. Recently, we demonstrated that BCL-6 is expressed at high levels in germinal center B-cells as a 92-98 kDa nuclear protein in a constitutively phosphorylated form. In this study, we show that BCL-6 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro at the sites phosphorylated in vivo. These numerous phosphorylation sites were found to be located in its serine- and proline-clustered (SPC) region (amino acids-250-483). BCL-6 phosphorylation significantly increased in Ramos cells following stimulation with 12-o-tetradecanoylphorbol-13-acetate (TPA) or BCL-6- and erk1-transfected COS-7 cells stimulated with epidermal growth factor (EGF), and the increase of phosphorylation was inhibited by MEK1 inhibitor, PD98059. Furthermore, we observed that BCL-6 was associated with MAPK in vivo and its SPC region was important for this association. These results suggest that the functions of BCL-6 are regulated by phosphorylation mediated by the MAPK signaling pathway.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Moriyama, M., Yamochi, T., Semba, K. et al. BCL-6 is phosphorylated at multiple sites in its serine- and proline-clustered region by mitogen-activated protein kinase (MAPK) in vivo. Oncogene 14, 2465–2474 (1997). https://doi.org/10.1038/sj.onc.1201084
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201084
Keywords
This article is cited by
-
Feedback regulation of lymphocyte signalling
Nature Reviews Immunology (2004)
-
Ambivalent role of BCL6 in cell survival and transformation
Oncogene (2003)
-
Overexpressed BCL6 (LAZ3) oncoprotein triggers apoptosis, delays S phase progression and associates with replication foci
Oncogene (1999)
-
Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death accompanied by down-regulation of BCL-2 and BCL-XL
Oncogene (1999)