Baron Beverly W, Zeleznik-Le Nancy, Baron Miriam J, Theisler Catherine, Huo Dezheng, Krasowski Matthew D, Thirman Michael J, Baron Rebecca M, Baron Joseph M
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7449-54. doi: 10.1073/pnas.0701770104. Epub 2007 Apr 27.
The human BCL6 gene on chromosome 3 band q27, which encodes a transcriptional repressor, is implicated in the pathogenesis of human lymphomas, especially the diffuse large B-cell type. We previously identified the human PDCD2 (programmed cell death-2) gene as a target of BCL6 repression. PDCD2 encodes a protein that is expressed in many human tissues, including lymphocytes, and is known to interact with corepressor complexes. We now show that BCL6 can bind directly to the PDCD2 promoter, repressing its transcription. Knockdown of endogenous BCL6 in a human B cell lymphoma line by introduction of small interfering RNA duplexes increases PDCD2 protein expression. Furthermore, there is an inverse relationship between the expression levels of the BCL6 and PDCD2 proteins in the lymphoid tissues of mice overexpressing human BCL6 (high BCL6 levels, minimal PDCD2) and controls (minimal BCL6, high PDCD2) as well as in tissues examined from some human B and T cell lymphomas. These data confirm PDCD2 as a target of BCL6 and support the concept that repression of PDCD2 by BCL6 is likely important in the pathogenesis of certain human lymphomas.
位于3号染色体q27带的人类BCL6基因编码一种转录抑制因子，与人类淋巴瘤尤其是弥漫性大B细胞型淋巴瘤的发病机制有关。我们之前鉴定出人类PDCD2（程序性细胞死亡2）基因是BCL6的抑制靶点。PDCD2编码一种在包括淋巴细胞在内的多种人类组织中表达的蛋白质，已知其能与共抑制复合物相互作用。我们现在表明，BCL6可直接结合至PDCD2启动子，抑制其转录。通过导入小干扰RNA双链体在人B细胞淋巴瘤系中敲低内源性BCL6可增加PDCD2蛋白表达。此外，在过表达人类BCL6的小鼠（BCL6水平高，PDCD2最低）和对照小鼠（BCL6最低，PDCD2高）的淋巴组织以及一些人类B细胞和T细胞淋巴瘤的检测组织中，BCL6和PDCD2蛋白的表达水平呈负相关。这些数据证实PDCD2是BCL6的靶点，并支持BCL6对PDCD2的抑制在某些人类淋巴瘤发病机制中可能很重要这一观点。
