FOXO-regulated transcription restricts overgrowth of Tsc mutant organs

被引：39

作者：

Harvey, Kieran F. ^{[1
,2
,5
]}

Mattila, Jaakko ^{[3
]}

Sofer, Avi ^{[4
]}

Bennett, F. Christian ^{[1
,2
]}

Ramsey, Matthew R. ^{[4
]}

Ellisen, Leif W. ^{[4
]}

Puig, Oscar ^{[3
]}

Hariharan, Iswar K. ^{[5
]}

机构：

[1] Peter MacCallum Canc Ctr, Cell Growth & Proliferat Lab, Melbourne, Vic 3002, Australia

[2] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia

[3] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland

[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA

[5] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

来源：

JOURNAL OF CELL BIOLOGY | 2008年 / 180卷 / 04期

关键词：

D O I：

10.1083/jcb.200710100

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

FOXO is thought to function as a repressor of growth that is, in turn, inhibited by insulin signaling. However, inactivating mutations in Drosophila melanogaster FOXO result in viable flies of normal size, which raises a question over the involvement of FOXO in growth regulation. Previously, a growth-suppressive role for FOXO under conditions of increased target of rapamycin (TOR) pathway activity was described. Here, we further characterize this phenomenon. We show that tuberous sclerosis complex 1 mutations cause increased FOXO levels, resulting in elevated expression of FOXO-regulated genes, some of which are known to antagonize growth-promoting pathways. Analogous transcriptional changes are observed in mammalian cells, which implies that FOXO attenuates TOR-driven growth in diverse species.

引用

页码：691 / 696

页数：6

共 29 条

[1] Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway [J].