作者
Steven J Bensinger, Michelle N Bradley, Sean B Joseph, Noam Zelcer, Edith M Janssen, Mary Ann Hausner, Roger Shih, John S Parks, Peter A Edwards, Beth D Jamieson, Peter Tontonoz
发表日期
2008/7/11
期刊
Cell
卷号
134
期号
1
页码范围
97-111
出版商
Elsevier
简介
Cholesterol is essential for membrane synthesis; however, the mechanisms that link cellular lipid metabolism to proliferation are incompletely understood. We demonstrate here that cellular cholesterol levels in dividing T cells are maintained in part through reciprocal regulation of the LXR and SREBP transcriptional programs. T cell activation triggers induction of the oxysterol-metabolizing enzyme SULT2B1, consequent suppression of the LXR pathway for cholesterol transport, and promotion of the SREBP pathway for cholesterol synthesis. Ligation of LXR during T cell activation inhibits mitogen-driven expansion, whereas loss of LXRβ confers a proliferative advantage. Inactivation of the sterol transporter ABCG1 uncouples LXR signaling from proliferation, directly linking sterol homeostasis to the antiproliferative action of LXR. Mice lacking LXRβ exhibit lymphoid hyperplasia and enhanced responses to antigenic …
引用总数
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