| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 279, Issue 2, 1513-1525, January 9, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
||
From the
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, the Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea, and the ¶Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215
FLICE-inhibitory protein (FLIP) is a homolog of caspase-8 that lacks catalytic activity and has been shown to be important in protecting endothelial cells from apoptosis. The serine/threonine kinase Akt/PKB was recently reported to promote FLIP expression in endothelial and tumor cells. Here we examined the role of the forkhead transcription factor FOXO3a, a downstream target of Akt, in controlling FLIP regulation in endothelial cells. FOXO3a nuclear translocation was regulated by Akt in human umbilical vein endothelial cells. Transduction of a nonphosphorylatable, constitutively active mutant of FOXO3a (TM-FOXO3a) led to the down-regulation of FLIP levels. Transduction with TM-FOXO3a also increased caspase-8 activity and promoted apoptosis in endothelial cells. Conversely, transduction of a dominant-negative mutant of FOXO3a up-regulated FLIP levels and protected endothelial cells from apoptosis under serum deprivation conditions. Restoration of intracellular FLIP blocked caspase-8 activation and inhibited apoptosis in TM-FOXO3a-transduced cells. These data suggest that FOXO3a is a downstream target of Akt in endothelial cells that can promote apoptosis via FLIP down-regulation and activation of the extrinsic apoptotic pathway.
Received for publication, May 6, 2003 , and in revised form, September 17, 2003.
* This work was supported by National Institutes of Health Grants AG15052, AR40197, AG17291, and HL72108. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|| To whom correspondence should be addressed: Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany St., W611, Boston, MA 02118. Tel.: 617-414-2392; Fax: 617-414-2391; E-mail: kxwalsh{at}bu.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. X. Fang, F. Dong, D. P. Thomas, H. Ma, L. He, and J. Ren Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1206 - H1215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ueffing, M. Schuster, E. Keil, K. Schulze-Osthoff, and I. Schmitz Up-regulation of c-FLIPshort by NFAT contributes to apoptosis resistance of short-term activated T cells Blood, August 1, 2008; 112(3): 690 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Allard, N. Figg, M. R. Bennett, and T. D. Littlewood Akt Regulates the Survival of Vascular Smooth Muscle Cells via Inhibition of FoxO3a and GSK3 J. Biol. Chem., July 11, 2008; 283(28): 19739 - 19747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. B. Choi and J. Nicholas Autocrine and Paracrine Promotion of Cell Survival and Virus Replication by Human Herpesvirus 8 Chemokines J. Virol., July 1, 2008; 82(13): 6501 - 6513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Juhasz, M. Thirunavukkarasu, R. Pant, L. Zhan, S. V. Penumathsa, E. R. Secor Jr., S. Srivastava, U. Raychaudhuri, V. P. Menon, H. Otani, et al. Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1365 - H1370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Laguinge, R. N. Samara, W. Wang, W. S. El-Deiry, G. Corner, L. Augenlicht, L. Mishra, and J. M. Jessup DR5 Receptor Mediates Anoikis in Human Colorectal Carcinoma Cell Lines Cancer Res., February 1, 2008; 68(3): 909 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Lee, H.-J. You, J.-Y. Won, S.-W. Youn, H.-J. Cho, K.-W. Park, W.-Y. Park, J.-S. Seo, Y.-B. Park, K. Walsh, et al. Forkhead Factor, FOXO3a, Induces Apoptosis of Endothelial Cells Through Activation of Matrix Metalloproteinases Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 302 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Papanicolaou, Y. Izumiya, and K. Walsh Forkhead Transcription Factors and Cardiovascular Biology Circ. Res., January 4, 2008; 102(1): 16 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Lee, S.-W. Youn, J.-Y. Kim, K.-W. Park, C.-I. Hwang, W.-Y. Park, B.-H. Oh, Y.-B. Park, K. Walsh, J.-S. Seo, et al. FOXO3a Turns the Tumor Necrosis Factor Receptor Signaling Towards Apoptosis Through Reciprocal Regulation of c-Jun N-Terminal Kinase and NF-{kappa}B Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 112 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yoshida, K. Murao, H. Imachi, W. M. Cao, X. Yu, J. Li, R. A. M. Ahmed, N. Kitanaka, N. C. W. Wong, T. G. Unterman, et al. Pancreatic Glucokinase Is Activated by Insulin-Like Growth Factor-I Endocrinology, June 1, 2007; 148(6): 2904 - 2913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yu, K. Murao, H. Imachi, W.-M. Cao, J. Li, K. Matsumoto, T. Nishiuchi, R. A.M. Ahmed, N. C.W. Wong, H. Kosaka, et al. Regulation of Scavenger Receptor Class BI Gene Expression by Angiotensin II in Vascular Endothelial Cells Hypertension, June 1, 2007; 49(6): 1378 - 1384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Li, X. Zhang, and A. F. Olumi MG-132 Sensitizes TRAIL-Resistant Prostate Cancer Cells by Activating c-Fos/c-Jun Heterodimers and Repressing c-FLIP(L) Cancer Res., March 1, 2007; 67(5): 2247 - 2255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Md. R. Abid, S.-C. Shih, H. H. Otu, K. C. Spokes, Y. Okada, D. T. Curiel, T. Minami, and W. C. Aird A Novel Class of Vascular Endothelial Growth Factor-responsive Genes That Require Forkhead Activity for Expression J. Biol. Chem., November 17, 2006; 281(46): 35544 - 35553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kajihara, M. Jones, L. Fusi, M. Takano, F. Feroze-Zaidi, G. Pirianov, H. Mehmet, O. Ishihara, J. M. Higham, E. W.-F. Lam, et al. Differential Expression of FOXO1 and FOXO3a Confers Resistance to Oxidative Cell Death upon Endometrial Decidualization Mol. Endocrinol., October 1, 2006; 20(10): 2444 - 2455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Shen, N. S. Brown, P. F. Finn, J. F. Dice, and H. A. Franch Akt and Mammalian Target of Rapamycin Regulate Separate Systems of Proteolysis in Renal Tubular Cells J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2414 - 2423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zeuner, F. Pedini, M. Signore, G. Ruscio, C. Messina, A. Tafuri, G. Girelli, C. Peschle, and R. De Maria Increased death receptor resistance and FLIPshort expression in polycythemia vera erythroid precursor cells Blood, May 1, 2006; 107(9): 3495 - 3502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. M. Tjin, R. W. J. Groen, I. Vogelzang, P. W. B. Derksen, M. D. Klok, H. P. Meijer, S. van Eeden, S. T. Pals, and M. Spaargaren Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma Blood, January 15, 2006; 107(2): 760 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Md. R. Abid, K. Yano, S. Guo, V. I. Patel, G. Shrikhande, K. C. Spokes, C. Ferran, and W. C. Aird Forkhead Transcription Factors Inhibit Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia J. Biol. Chem., August 19, 2005; 280(33): 29864 - 29873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Poukkula, A. Kaunisto, V. Hietakangas, K. Denessiouk, T. Katajamaki, M. S. Johnson, L. Sistonen, and J. E. Eriksson Rapid Turnover of c-FLIPshort Is Determined by Its Unique C-terminal Tail J. Biol. Chem., July 22, 2005; 280(29): 27345 - 27355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Skurk, Y. Izumiya, H. Maatz, P. Razeghi, I. Shiojima, M. Sandri, K. Sato, L. Zeng, S. Schiekofer, D. Pimentel, et al. The FOXO3a Transcription Factor Regulates Cardiac Myocyte Size Downstream of AKT Signaling J. Biol. Chem., May 27, 2005; 280(21): 20814 - 20823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Krippner-Heidenreich, G. Walsemann, M. J. Beyrouthy, S. Speckgens, R. Kraft, H. Thole, R. V. Talanian, M. M. Hurt, and B. Luscher Caspase-Dependent Regulation and Subcellular Redistribution of the Transcriptional Modulator YY1 during Apoptosis Mol. Cell. Biol., May 1, 2005; 25(9): 3704 - 3714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Giresi, E. J. Stevenson, J. Theilhaber, A. Koncarevic, J. Parkington, R. A. Fielding, and S. C. Kandarian Identification of a molecular signature of sarcopenia Physiol Genomics, April 14, 2005; 21(2): 253 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-W. Park, D.-H. Kim, H.-J. You, J.-J. Sir, S.-I. Jeon, S.-W. Youn, H.-M. Yang, C. Skurk, Y.-B. Park, K. Walsh, et al. Activated Forkhead Transcription Factor Inhibits Neointimal Hyperplasia After Angioplasty Through Induction of p27 Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 742 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alikhani, Z. Alikhani, and D. T. Graves FOXO1 Functions as a Master Switch That Regulates Gene Expression Necessary for Tumor Necrosis Factor-induced Fibroblast Apoptosis J. Biol. Chem., April 1, 2005; 280(13): 12096 - 12102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Guo and G. E. Sonenshein Forkhead Box Transcription Factor FOXO3a Regulates Estrogen Receptor Alpha Expression and Is Repressed by the Her-2/neu/Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Mol. Cell. Biol., October 1, 2004; 24(19): 8681 - 8690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, K. Sato, T. Aprahamian, N. J. Brown, J. Hutcheson, A. Bialik, H. Perlman, and K. Walsh Endothelial Overexpression of Fas Ligand Decreases Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1466 - 1473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Skurk and K. Walsh Death Receptor Induced Apoptosis: A New Mechanism of Homocysteine-Mediated Endothelial Cell Cytotoxicity Hypertension, June 1, 2004; 43(6): 1168 - 1170. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
