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

Authors:
Lin-Lee YC, Pham LV, Tamayo AT, Fu L, Zhou HJ, Yoshimura LC, Decker GL, Ford RJ
In:
Source: J Biol Chem
Publication Date: (2006)
Issue: 281(27): 18878-87
Research Area:
Immunotherapy / Hematology
Cells used in publication:
B cell, human
Species: human
Tissue Origin: blood
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
CD40 is a TNF receptor superfamily (TNRSF-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-GFP fusion-protein entered B-cell nuclei. The CD40 protein contains a nuclear localization signal (NLS) sequence, that when mutated, blocks entry of CD40 into the nucleus through the classic karyopherins (Importins-a/sspathway). 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. CD40, another TNF family member, involved in cell survival in the B cell linkage, like other nuclear growth factor receptors, 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.