这种BCL6原瘤基因抑制了生殖中心B细胞中的p53表达
Ryan T Phan1, Riccardo Dalla-Favera
1Institute for Cancer Genetics and the Department of Pathology, Columbia University, New York, New York 10032, USA.
Nature
|December 4, 2004
概括
BCL6基因抑制p53瘤抑制剂,保护生殖中心B细胞免受DNA损伤诱导的亡. 这种机制对于正常的B细胞发育至关重要,并且在放松调节时可能导致B细胞淋巴瘤.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- BCL6原瘤基因对于生殖中心的形成至关重要,并且与B细胞淋巴瘤的发病相关.
- 由于对其直接点基因的鉴定有限,BCL6在生殖中心发育和淋巴发育中的确切作用仍然不清楚.
研究的目的:
- 研究BCL6在生殖中心B细胞中的功能,特别是其在调节p53瘤抑制基因表达和DNA损伤诱导的亡中的作用.
- 阐明BCL6影响B细胞存活的机制及其对淋巴发育的影响.
主要方法:
- 分析BCL6对生殖中心B细胞中p53表达的影响.
- 在p53促进体区域内识别BCL6结合部位.
- 使用短干扰RNA (siRNA) 抑制BCL6表达并评估p53水平.
- 评估BCL6对DNA损伤后B细胞系的亡的影响.
主要成果:
- BCL6通过结合p53促进体中的特定位点直接抑制p53转录.
- 在BCL6高度表达的生殖中心B细胞中,p53表达不存在.
- 抑制BCL6会导致p53mRNA和蛋白质水平的增加,特别是在对DNA损伤的反应中.
- 构成性BCL6表达赋予了B细胞系中对DNA损伤诱导的亡的抵抗力.
结论:
- BCL6使生殖中心B细胞能够在免疫球蛋白基因多样化过程中耐受DNA断裂,而不会触发p53依赖的亡.
- 失调的BCL6表达通过功能性地使p53瘤抑制路径无活化,有助于淋巴发育.
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