TY - JOUR
T1 - BCL-6 negatively regulates expression of the NF-κB1 p105/p50 subunit
AU - Li, Zhiping
AU - Wang, Xing
AU - Yu, Raymond Yick Loi
AU - Ding, B. Belinda
AU - Yu, J. Jessica
AU - Dai, Xu Ming
AU - Naganuma, Akira
AU - Stanley, E. Richard
AU - Ye, B. Hilda
PY - 2005/1/1
Y1 - 2005/1/1
N2 - BCL-6 is a transcription repressor frequently deregulated in non-Hodgkin's B cell lymphomas. Its activity is also critical to germinal center development and balanced Th1/Th2 differentiation. Previous studies have suggested that NF-κB activity is suppressed in germinal center and lymphoma B cells that express high levels of BCL-6, and yet the reason for this is unknown. We report in this study that BCL-6 can bind to three sequence motifs in the 5′ regulatory region of NF-κB1 in vitro and in vivo, and repress NF-κB1 transcription both in reporter assays and in lymphoma B cell lines. BCL-6 -/- mice further confirm the biological relevance of BCL-6-dependent regulation of NF-κB1 because BCL-6 inactivation caused notable increase in p105/p50 proteins in several cell types. Among these, BCL-6-/- macrophage cell lines displayed a hyperproliferation phenotype that can be reversed by NF-κB inhibitors, e.g., N-tosyl-L-phenylalanine chloromethyl ketone and SN50, a result that is consistent with increased nuclear κB-binding activity of p50 homodimer and p50/p65 heterodimer. Our results demonstrate that BCL-6 can negatively regulate NF-κB1 expression, thereby inhibiting NF-κB-mediated cellular functions. The Journal of Immunology, 2005, 174: 205-214.
AB - BCL-6 is a transcription repressor frequently deregulated in non-Hodgkin's B cell lymphomas. Its activity is also critical to germinal center development and balanced Th1/Th2 differentiation. Previous studies have suggested that NF-κB activity is suppressed in germinal center and lymphoma B cells that express high levels of BCL-6, and yet the reason for this is unknown. We report in this study that BCL-6 can bind to three sequence motifs in the 5′ regulatory region of NF-κB1 in vitro and in vivo, and repress NF-κB1 transcription both in reporter assays and in lymphoma B cell lines. BCL-6 -/- mice further confirm the biological relevance of BCL-6-dependent regulation of NF-κB1 because BCL-6 inactivation caused notable increase in p105/p50 proteins in several cell types. Among these, BCL-6-/- macrophage cell lines displayed a hyperproliferation phenotype that can be reversed by NF-κB inhibitors, e.g., N-tosyl-L-phenylalanine chloromethyl ketone and SN50, a result that is consistent with increased nuclear κB-binding activity of p50 homodimer and p50/p65 heterodimer. Our results demonstrate that BCL-6 can negatively regulate NF-κB1 expression, thereby inhibiting NF-κB-mediated cellular functions. The Journal of Immunology, 2005, 174: 205-214.
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U2 - 10.4049/jimmunol.174.1.205
DO - 10.4049/jimmunol.174.1.205
M3 - Article
C2 - 15611242
AN - SCOPUS:10844275574
SN - 0022-1767
VL - 174
SP - 205
EP - 214
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -