Nuclear localization in the biology of the CD40 receptor in normal and neoplastic human B lymphocytes

Yen Chiu Lin-Lee, Lan V. Pham, Archito T. Tamayo, Lingchen Fu, Hai Jun Zhou, Linda C. Yoshimura, Glenn L. Decker, Richard J. Ford*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

CD40 is a tumor necrosis factor (TNF) receptor superfamily, (TNFR; TNFRSF-5) member, that initiates important signaling pathways mediating cell growth, survival, and differentiation in B-lymphocytes. Although CD40 has been extensively studied as a plasma membrane-associated growth factor receptor, we demonstrate here that CD40 is present not only in the plasma membrane and cytoplasm but also in the nucleus of normal and neoplastic B-lymphoid cells. Confocal microscopy showed that transfected CD40-green fluorescent fusion protein entered B-cell nuclei. The CD40 protein contains a nuclear localization signal sequence that, when mutated, blocks entry of CD40 into the nucleus through the classic karyopherins (importins-α/β) pathway. Nuclear fractionation studies revealed the presence of CD40 protein in the nucleoplasm fraction of activated B cells, and chromatin immunoprecipitation assays demonstrated that CD40 binds to and stimulates the BLyS/BAFF promoter, another TNF family member (TNFSF-13B) involved in cell survival in the B cell lineage. Like other nuclear growth factor receptors, CD40 appears to be a transcriptional regulator and is likely to play a larger and more complex role than previously demonstrated in regulating essential growth and survival pathways in B-lymphocytes.

Original languageEnglish (US)
Pages (from-to)18878-18887
Number of pages10
JournalJournal of Biological Chemistry
Volume281
Issue number27
DOIs
StatePublished - Jul 7 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lin-Lee, Y. C., Pham, L. V., Tamayo, A. T., Fu, L., Zhou, H. J., Yoshimura, L. C., Decker, G. L., & Ford, R. J. (2006). Nuclear localization in the biology of the CD40 receptor in normal and neoplastic human B lymphocytes. Journal of Biological Chemistry, 281(27), 18878-18887. https://doi.org/10.1074/jbc.M513315200