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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sunayama, Jun Masuyama, Norihisa Tsuruta, Fuminori Gotoh, Yukiko |
| Description | Author Affiliation: Sunayama J ( Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.) |
| Abstract | Life and death decisions are made by integrating a variety of apoptotic and survival signals in mammalian cells. Therefore, there is likely to be a common mechanism that integrates multiple signals adjudicating between the alternatives. In this study, we propose that 14-3-3 represents such an integration point. Several proapoptotic proteins commonly become associated with 14-3-3 upon phosphorylation by survival-mediating kinases such as Akt. We reported previously that cellular stresses induce c-Jun $NH_{2}-terminal$ kinase (JNK)–mediated 14-3-3ζ phosphorylation at Ser184 (Tsuruta, F., J. Sunayama, Y. Mori, S. Hattori, S. Shimizu, Y. Tsujimoto, K. Yoshioka, N. Masuyama, and Y. Gotoh. 2004. EMBO J. 23:1889–1899). Here, we show that phosphorylation of 14-3-3 by JNK releases the proapoptotic proteins Bad and FOXO3a from 14-3-3 and antagonizes the effects of Akt signaling. As a result of dissociation, Bad is dephosphorylated and translocates to the mitochondria, where it associates with $Bcl-2/Bcl-x_{L}.$ Because Bad and FOXO3a share the 14-3-3–binding motif with other proapoptotic proteins, we propose that this JNK-mediated phosphorylation of 14-3-3 regulates these proapoptotic proteins in concert and makes cells more susceptible to apoptotic signals. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 2 |
| Volume Number | 170 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2005-07-18 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | 14-3-3 Proteins Metabolism JNK Mitogen-Activated Protein Kinases Physiology Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Animals Apoptosis Binding Sites Carrier Proteins Cell Line Cell Survival Cercopithecus Aethiops Forkhead Transcription Factors Mitochondria Phosphorylation Protein Transport Proto-Oncogene Proteins C-akt Proto-Oncogene Proteins C-bcl-2 Signal Transduction Transcription Factors Bcl-Associated Death Protein Bcl-X Protein Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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