FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal

被引：343

作者：

You, Han

Pellegrini, Marc

Tsuchihara, Katsuya

Yamamoto, Kazuo

Hacker, Georg

Erlacher, Miriam

Villunger, Andreas

Mak, Tak W. ^{[1
]}

机构：

[1] Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada

[2] Univ Toronto, Dept Med Biophys & Immunol, Toronto, ON M5G 2M9, Canada

[3] Tech Univ Munich, Inst Med Microbiol, D-81675 Munich, Germany

[4] Innsbruck Med Univ, Bioctr, Div Expt Pathophysiol & Immunol, A-6020 Innsbruck, Austria

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2006年 / 203卷 / 07期

关键词：

D O I：

10.1084/jem.20060353

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Puma is an essential mediator of p53-dependent and -independent apoptosis in vivo. In response to genotoxic stress, Puma is induced in a p53-dependent manner. However, the transcription factor driving Puma up-regulation in response to p53-independent apoptotic stimuli has yet to be identified. Here, we show that FOXO3a up-regulates Puma expression in response to cytokine or growth factor deprivation. Importantly, dysregulated Akt signaling in lymphoid cells attenuated Puma induction upon cytokine withdrawal. Our results suggest that Puma, together with another BH3 only member, Bim, function as FOXO3a downstream targets to mediate a stress response when PI3K/Akt signaling is down-regulated.

引用

页码：1657 / 1663

页数：7

共 25 条

[1] Proapoptotic Bcl-2 relative bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity
Bouillet, P
Metcalf, D
Huang, DCS
Tarlinton, DM
Kay, TWH
Köntgen, F
Adams, JM
Strasser, A
[J]. SCIENCE, 1999, 286 (5445) : 1735 - 1738
[2] Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)
Brunet, A
Park, J
Tran, H
Hu, LS
Hemmings, BA
Greenberg, ME
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (03) : 952 - 965
[3] Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor
Brunet, A
Bonni, A
Zigmond, MJ
Lin, MZ
Juo, P
Hu, LS
Anderson, MJ
Arden, KC
Blenis, J
Greenberg, ME
[J]. CELL, 1999, 96 (06) : 857 - 868
[4] Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene
Chen, WS
Xu, PZ
Gottlob, K
Chen, ML
Sokol, K
Shiyanova, T
Roninson, I
Weng, W
Suzuki, R
Tobe, K
Kadowaki, T
Hay, N
[J]. GENES & DEVELOPMENT, 2001, 15 (17) : 2203 - 2208
[5] THYMOCYTE APOPTOSIS INDUCED BY P53-DEPENDENT AND INDEPENDENT PATHWAYS
CLARKE, AR
PURDIE, CA
HARRISON, DJ
MORRIS, RG
BIRD, CC
HOOPER, ML
WYLLIE, AH
[J]. NATURE, 1993, 362 (6423) : 849 - 852
[6] Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis
Cully, M
You, H
Levine, AJ
Mak, TW
[J]. NATURE REVIEWS CANCER, 2006, 6 (03) : 184 - 192
[7] FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK
Essers, MAG
Weijzen, S
de Vries-Smits, AMM
Saarloos, I
de Ruiter, ND
Bos, JL
Burgering, BMT
[J]. EMBO JOURNAL, 2004, 23 (24) : 4802 - 4812
[8] Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals
Han, JW
Flemington, C
Houghton, AB
Gu, ZM
Zambetti, GP
Lutz, RJ
Zhu, L
Chittenden, T
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (20) : 11318 - 11323
[9] Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification
Hosaka, T
Biggs, WH
Tieu, D
Boyer, AD
Varki, NM
Cavenee, WK
Arden, KC
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) : 2975 - 2980
[10] Puma is an essential mediator of p53-dependent and -independent apoptotic pathways
Jeffers, JR
Parganas, E
Lee, Y
Yang, CY
Wang, JL
Brennan, J
MacLean, KH
Han, JW
Chittenden, T
Ihle, JN
McKinnon, PJ
Cleveland, JL
Zambetti, GP
[J]. CANCER CELL, 2003, 4 (04) : 321 - 328

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