期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 442, 期 3-4, 页码 177-182出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.11.046
关键词
Kaiso; Bcl6; B cell; Germinal center; Spleen; Splenomegaly; Cell proliferation
资金
- DOYAK Research Grant from the National Research Foundation (NRF) of the Korean Ministry of Education, Science and Technology [2011-0028817]
- National Research Foundation of Korea [2011-0028817] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Kaiso was previously described as a methylated DNA-binding protein and a transcription repressor interacting with the corepressor protein complex NCoR In the current study, we show that generation-3 Kaiso knockout mice show a phenotype of splenomegaly and large diffused germinal centers (GC). In the spleens of Kaiso knockout mice, Bcl6 (a transcriptional repressor that plays a critical role in GC development in spleen) and c-Myc were highly expressed, while the cell cycle arrest genes p27 (CDKN1B), p21 (CDKN1A) and Gadd45a were downregulated. Chromatin immunoprecipitation (ChIP) and transcription assays suggested that Kaiso represses Bcl6 expression, and in Kaiso knockout mice, derepressed Bcl6 increased cell proliferation by suppressing p27 (CDKN1B), p21 (CDKN1A) and Gadd45a, while upregulating the oncogene c-Myc. Further evidence for Kaiso regulation of splenomegaly was provided by B lymphocyte Ramos cells, in which ectopic KAISO repressed BCL6 and c-MYC expression, while concomitantly increasing the expression of the cell cycle arrestors p21, p27 and Gadd45a. In summary, derepressed Bcl6 expression may be responsible for increases in GC cell proliferation and splenomegaly of Kaiso knockout mice. (C) 2013 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据