SEARCH:   Advanced

Blood, 7 May 2009, Vol. 113, No. 19, pp. 4627-4636. Prepublished online as a Blood First Edition Paper on March 3, 2009; DOI 10.1182/blood-2008-10-183467. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-10-183467v1 113/19/4627    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fu, L. Articles by Ford, R. J. Search for Related Content PubMed PubMed Citation Articles by Fu, L. Articles by Ford, R. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 9, 2008 Accepted February 9, 2009 BAFF-R promotes cell proliferation and survival through interaction with IKK and NF-B/c-Rel in the nucleus of normal and neoplastic B lymphoid cells Lingchen Fu, Yen-Chiu Lin-Lee, Lan V. Pham, Archito T. Tamayo, Linda C. Yoshimura, and Richard J. Ford* Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States * Corresponding author; email: rford{at}mdanderson.org. BLyS and its major receptor BAFF-R, have been shown to be critical for development and homeostasis of normal B-lymphocytes, and for cell growth and survival of neoplastic B-lymphocytes, but the biologic mechanisms of this ligand/receptor-derived intracellular signaling pathway(s) have not been completely defined. We have discovered that the BAFF-R protein was present in the cell nucleus, in addition to its integral presence in the plasma membrane and cytoplasm, in both normal and neoplastic B-cells. BAFF-R interacted with histone H3 and IKK in the cell nucleus, enhancing histone H3 phosphorylation through IKK. Nuclear BAFF-R was also associated with NF-B/c-Rel and bound to NF-B targeted promoters including BLyS, CD154, Bcl-xL, IL-8, and Bfl-1/A1, promoting the transcription of these genes. These observations suggested that in addition to activating NF-B pathways in the plasma membrane, BAFF-R also promotes normal B-cell and NHL-B cell survival and proliferation by functioning as a transcriptional regulator through a chromatin remodeling mechanism(s) and NF-B association. Our studies provide an expanded conceptual view of the BAFF-R signaling, that should contribute a better understanding of the physiologic mechanisms involved in normal B-cell survival and growth, as well as in the pathophysiology of aggressive B-cell malignancies and autoimmune diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. N. Khan B Cell Receptor and BAFF Receptor Signaling Regulation of B Cell Homeostasis J. Immunol., September 15, 2009; 183(6): 3561 - 3567. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020