PMID- 17567982
OWN - NLM
STAT- MEDLINE
DCOM- 20071030
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 110
IP  - 6
DP  - 2007 Sep 15
TI  - Nuclear CD40 interacts with c-Rel and enhances proliferation in aggressive B-cell 
      lymphoma.
PG  - 2121-7
AB  - CD40 is an integral plasma membrane-associated member of the TNF receptor family 
      that has recently been shown to also reside in the nucleus of both normal B cells 
      and large B-cell lymphoma (LBCL) cells. However, the physiological function of 
      CD40 in the B-cell nucleus has not been examined. In this study, we demonstrate 
      that nuclear CD40 interacts with the NF-kappaB protein c-Rel, but not p65, in 
      LBCL cells. Nuclear CD40 forms complexes with c-Rel on the promoters of NF-kappaB 
      target genes, CD154, BLyS/BAFF, and Bfl-1/A1, in various LBCL cell lines. 
      Wild-type CD40, but not NLS-mutated CD40, further enhances c-Rel-mediated Blys 
      promoter activation as well as proliferation in LBCL cells. Studies in normal B 
      cells and LBCL patient cells further support a nuclear transcriptional function 
      for CD40 and c-Rel. Cooperation between nuclear CD40 and c-Rel appears to be 
      important in regulating cell growth and survival genes involved in lymphoma cell 
      proliferation and survival mechanisms. Modulating the nuclear function of CD40 
      and c-Rel could reveal new mechanisms in LBCL pathophysiology and provide 
      potential new targets for lymphoma therapy.
FAU - Zhou, Hai-Jun
AU  - Zhou HJ
AD  - Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Pham, Lan V
AU  - Pham LV
FAU - Tamayo, Archito T
AU  - Tamayo AT
FAU - Lin-Lee, Yen-Chiu
AU  - Lin-Lee YC
FAU - Fu, Lingchen
AU  - Fu L
FAU - Yoshimura, Linda C
AU  - Yoshimura LC
FAU - Ford, Richard J
AU  - Ford RJ
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - CA-16672-26/CA/NCI NIH HHS/United States
GR  - CA-R01-100836/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070613
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (B-Cell Activating Factor)
RN  - 0 (CD40 Antigens)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
CIN - Blood. 2007 Sep 15;110(6):1710-1
MH  - B-Cell Activating Factor/genetics/metabolism
MH  - B-Lymphocytes/metabolism
MH  - CD40 Antigens/genetics/*metabolism
MH  - Cell Nucleus/*metabolism
MH  - *Cell Proliferation
MH  - Chromatin Immunoprecipitation
MH  - Electrophoretic Mobility Shift Assay
MH  - Genes, rel/*physiology
MH  - Humans
MH  - Immunoprecipitation
MH  - Luciferases/metabolism
MH  - Lymphoma, B-Cell/genetics/*metabolism/pathology
MH  - Lymphoma, Large B-Cell, Diffuse/genetics/*metabolism/pathology
MH  - Promoter Regions, Genetic
MH  - Thymidine/metabolism
MH  - Transfection
MH  - beta-Galactosidase/metabolism
PMC - PMC1976364
EDAT- 2007/06/15 09:00
MHDA- 2007/10/31 09:00
PMCR- 2008/09/15
CRDT- 2007/06/15 09:00
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2007/10/31 09:00 [medline]
PHST- 2007/06/15 09:00 [entrez]
PHST- 2008/09/15 00:00 [pmc-release]
AID - S0006-4971(20)60608-5 [pii]
AID - 2007/073080 [pii]
AID - 10.1182/blood-2007-02-073080 [doi]
PST - ppublish
SO  - Blood. 2007 Sep 15;110(6):2121-7. doi: 10.1182/blood-2007-02-073080. Epub 2007 
      Jun 13.