期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 24, 页码 10175-10180出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0704170104
关键词
gene regulation; lymphomagenesis; signal transduction
资金
- NCI NIH HHS [R01 CA090571, CA 107300, CA 90571, R01 CA107300] Funding Source: Medline
- NEI NIH HHS [PN/EY 018228] Funding Source: Medline
- NIGMS NIH HHS [R43 GM085841, R44 GM085841, GM 07185, GM 85841, GM 073981, T32 GM007185, R01 GM040185, R01 GM073981, GM 040185] Funding Source: Medline
Aberrant expression of the TCL1 oncoprotein promotes malignant transformation of germinal center (GC) B cells. Repression of TCL1 in GC B cells facilitates FAS-mediated apoptosis and prevents lymphoma formation. However, the mechanism for this repression is unknown. Here we show that the CREB coactivator TORC2 directly regulates TCL1 expression independent of CREB Ser-133 phosphorylation and CBP/p300 recruitment. GC signaling through CD40 or the BCR, which activates pCREB-dependent genes, caused TORC2 phosphorylation, cytosolic emigration, and TCL1 repression. Signaling via cAMP-inducible pathways inhibited TCL1 repression and reduced apoptosis, consistent with a prosurvival role for TCL1 before GC selection and supporting an initiating role for aberrant TCL1 expression during GC lymphomagenesis. Our data indicate that a novel CREB/TORC2 regulatory mode controls the normal program of GC gene activation and repression that promotes B cell development and circumvents oncogenic progression. Our results also reconcile a paradox in which signals that activate pCREB/CBP/ p300 genes concurrently repress TCL1 to initiate its silencing.
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