A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR

被引：365

作者：

Ramaswamy, S

Nakamura, N

Sansal, I

Bergeron, L

Sellers, WR ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Internal Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Millennium Pharmaceut, Div Oncol, Cambridge, MA 02139 USA

来源：

CANCER CELL | 2002年 / 2卷 / 01期

关键词：

D O I：

10.1016/S1535-6108(02)00086-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The mammalian DAF-16-like transcription factors, FKHR, FKHRL1, and AFX, function as key regulators of insulin signaling, cell cycle progression, and apoptosis downstream of phosphoinositide 3-kinase. Gene activation through binding to insulin response sequences (IRS) has been thought to be essential for mediating these functions. However, using transcriptional profiling, chromatin immunoprecipitation, and functional experiments, we demonstrate that rather than activation of IRS regulated genes (Class I transcripts), transcriptional repression of D-type cyclins (in Class 111) is required for FKHR mediated inhibition of cell cycle progression and transformation. These data suggest that a novel mechanism of FKHR-mediated gene regulation is linked to its activity as a suppressor of tumor growth.

引用

页码：81 / 91

页数：11

共 45 条

[1] Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters - Transcription factor FKHR binds the insulin response sequence [J].