TY - JOUR
T1 - Negative autoregulation of BCL-6 is bypassed by genetic alterations in diffuse large B cell lymphomas
AU - Wang, Xing
AU - Li, Zhiping
AU - Naganuma, Akira
AU - Ye, B. Hilda
PY - 2002/11/12
Y1 - 2002/11/12
N2 - Thirty to forty percent of diffuse large B cell lymphomas (DLBCL) carry BCL-6 translocations that disrupt its 5′ regulatory region. This same region is also subject to somatic hypermutations, although only a small fraction of these mutations have a detectable effect on transcription. Here, we show that transcription of the BCL-6 gene is negatively self-regulated in multiple cell types. This mechanism operates by means of the interaction of two BCL-6-binding sites within exon 1 of the gene and the BCL-6 protein itself, which is a potent transcription repressor. Because the DLBCL-associated "activating mutations" specifically target these exon 1 binding sites, and because the entire exon 1 is usually removed in the BCL-6-translocated tumors, this autoregulation is bypassed in 30-40% of all DLBCL cases. Our results not only demonstrate an important mechanism governing the expression of BCL-6, but also explain how BCL-6 is deregulated in a large number of DLBCL patients, providing a better understanding of BCL-6-related lymphomagenesis.
AB - Thirty to forty percent of diffuse large B cell lymphomas (DLBCL) carry BCL-6 translocations that disrupt its 5′ regulatory region. This same region is also subject to somatic hypermutations, although only a small fraction of these mutations have a detectable effect on transcription. Here, we show that transcription of the BCL-6 gene is negatively self-regulated in multiple cell types. This mechanism operates by means of the interaction of two BCL-6-binding sites within exon 1 of the gene and the BCL-6 protein itself, which is a potent transcription repressor. Because the DLBCL-associated "activating mutations" specifically target these exon 1 binding sites, and because the entire exon 1 is usually removed in the BCL-6-translocated tumors, this autoregulation is bypassed in 30-40% of all DLBCL cases. Our results not only demonstrate an important mechanism governing the expression of BCL-6, but also explain how BCL-6 is deregulated in a large number of DLBCL patients, providing a better understanding of BCL-6-related lymphomagenesis.
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U2 - 10.1073/pnas.232581199
DO - 10.1073/pnas.232581199
M3 - Article
C2 - 12407182
AN - SCOPUS:0037069331
SN - 0027-8424
VL - 99
SP - 15018
EP - 15023
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -