![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RESEARCH PAPER
1 Howard Hughes Medical Institute, Cancer Institute of New Jersey, Rutgers University, Piscataway, New Jersey 08854, USA , 2 Center for Advanced Biotechnology and Medicine, Cancer Institute of New Jersey, Rutgers University, Piscataway, New Jersey 08854, USA , 3 Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, New Jersey 08854, USA
Expression of adenovirus E1A deregulates cell proliferation to facilitate viral DNA replication, prompting the initiation of apoptosis signaled primarily through proapoptotic BAK in productively infected cells. We demonstrate here that in uninfected cells, BAK is complexed with the anti-apoptotic BCL-2 family member Myeloid Cell Leukemia 1 (MCL-1). E1A expression during infection resulted in the specific down-regulation of MCL-1 through destabilization of the protein and loss of the mRNA. Upon loss of the MCL-1-BAK complex, BAK complexed with either BAX in proapoptotic E1B mutant adenovirus-infected cells, or with the adenovirus BCL-2 homolog E1B 19K in cells infected with the wild-type virus in which apoptosis is inhibited. Loss of MCL-1 was required to initiate the apoptotic pathway in infected cells as restoration of MCL-1 expression rescued infected cells from E1A-induced apoptosis. Analogous to E1A expression, DNA damage down-regulates MCL-1, and adenovirus infection resulted in the accumulation of phosphorylated H2AX and ataxia-telangiectasia mutant protein (ATM), hallmarks of DNA double-strand breaks. Thus, MCL-1 may function by maintaining BAK in an inactive state, and the loss of MCL-1 upon activation of the DNA damage response, perhaps through replication stress induced in virus infected cells, may be required to initiate the apoptotic response.
[Keywords: Apoptosis; MCL-1; E1B 19K; adenovirus; DNA damage; BAK]
Received September 30, 2003; revised version accepted October 22, 2003.
4 Present address: Discovery Research, ViroPharma Incorporated, Exton, PA 19341, USA.
5 Corresponding author.
E-MAIL ewhite{at}cabm.rutgers.edu; FAX (732) 235-5795.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Zhou, M. Liu, Y. Zhai, and W. Xie The Antiapoptotic Role of Pregnane X Receptor in Human Colon Cancer Cells Mol. Endocrinol., April 1, 2008; 22(4): 868 - 880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Germain, J. Milburn, and V. Duronio MCL-1 Inhibits BAX in the Absence of MCL-1/BAX Interaction J. Biol. Chem., March 7, 2008; 283(10): 6384 - 6392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. F. Lee, P. E. Czabotar, M. F. van Delft, E. M. Michalak, M. J. Boyle, S. N. Willis, H. Puthalakath, P. Bouillet, P. M. Colman, D. C.S. Huang, et al. A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation J. Cell Biol., January 28, 2008; 180(2): 341 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chetoui, K. Sylla, J.-V. Gagnon-Houde, C. Alcaide-Loridan, D. Charron, R. Al-Daccak, and F. Aoudjit Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis Mol. Cancer Res., January 1, 2008; 6(1): 42 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Zheng, Y.-C. Tsai, P. Kadimcherla, R. Zhang, J. Shi, G. A. Oyler, and N. N. Boustany The C-Terminal Transmembrane Domain of Bcl-xL Mediates Changes in Mitochondrial Morphology Biophys. J., January 1, 2008; 94(1): 286 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nguyen, R. C. Marcellus, A. Roulston, M. Watson, L. Serfass, S. R. Murthy Madiraju, D. Goulet, J. Viallet, L. Belec, X. Billot, et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis PNAS, December 4, 2007; 104(49): 19512 - 19517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I-J. Leu and D. L. George Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria Genes & Dev., December 1, 2007; 21(23): 3095 - 3109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Subramanian, S. Vijayalingam, E. Lomonosova, L.-j. Zhao, and G. Chinnadurai Evidence for Involvement of BH3-Only Proapoptotic Members in Adenovirus-Induced Apoptosis J. Virol., October 1, 2007; 81(19): 10486 - 10495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Fritsch, G. Schneider, D. Saur, M. Scheibel, and R. M. Schmid Translational Repression of MCL-1 Couples Stress-induced eIF2{alpha} Phosphorylation to Mitochondrial Apoptosis Initiation J. Biol. Chem., August 3, 2007; 282(31): 22551 - 22562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wojciechowski, P. Tripathi, T. Bourdeau, L. Acero, H. L. Grimes, J. D. Katz, F. D. Finkelman, and D. A. Hildeman Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis J. Exp. Med., July 9, 2007; 204(7): 1665 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Karantza-Wadsworth, S. Patel, O. Kravchuk, G. Chen, R. Mathew, S. Jin, and E. White Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis Genes & Dev., July 1, 2007; 21(13): 1621 - 1635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kobayashi, S.-H. Lee, X. W. Meng, J. L. Mott, S. F. Bronk, N. W. Werneburg, R. W. Craig, S. H. Kaufmann, and G. J. Gores Serine 64 Phosphorylation Enhances the Antiapoptotic Function of Mcl-1 J. Biol. Chem., June 22, 2007; 282(25): 18407 - 18417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ding, X. He, J.-M. Hsu, W. Xia, C.-T. Chen, L.-Y. Li, D.-F. Lee, J.-C. Liu, Q. Zhong, X. Wang, et al. Degradation of Mcl-1 by {beta}-TrCP Mediates Glycogen Synthase Kinase 3-Induced Tumor Suppression and Chemosensitization Mol. Cell. Biol., June 1, 2007; 27(11): 4006 - 4017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Yang, V. Kaushal, S. V. Shah, and G. P. Kaushal Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1710 - F1717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ding, X. He, W. Xia, J.-M. Hsu, C.-T. Chen, L.-Y. Li, D.-F. Lee, J.-Y. Yang, X. Xie, J.-C. Liu, et al. Myeloid Cell Leukemia-1 Inversely Correlates with Glycogen Synthase Kinase-3{beta} Activity and Associates with Poor Prognosis in Human Breast Cancer Cancer Res., May 15, 2007; 67(10): 4564 - 4571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Uren, G. Dewson, L. Chen, S. C. Coyne, D. C.S. Huang, J. M. Adams, and R. M. Kluck Mitochondrial permeabilization relies on BH3 ligands engaging multiple prosurvival Bcl-2 relatives, not Bak J. Cell Biol., April 23, 2007; 177(2): 277 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shimazu, K. Degenhardt, A. Nur-E-Kamal, J. Zhang, T. Yoshida, Y. Zhang, R. Mathew, E. White, and M. Inouye NBK/BIK antagonizes MCL-1 and BCL-XL and activates BAK-mediated apoptosis in response to protein synthesis inhibition Genes & Dev., April 15, 2007; 21(8): 929 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Czabotar, E. F. Lee, M. F. van Delft, C. L. Day, B. J. Smith, D. C. S. Huang, W. D. Fairlie, M. G. Hinds, and P. M. Colman Structural insights into the degradation of Mcl-1 induced by BH3 domains PNAS, April 10, 2007; 104(15): 6217 - 6222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Adams and G. M. Cooper Rapid Turnover of Mcl-1 Couples Translation to Cell Survival and Apoptosis J. Biol. Chem., March 2, 2007; 282(9): 6192 - 6200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Brunelle, E. H. Shroff, H. Perlman, A. Strasser, C. T. Moraes, R. A. Flavell, N. N. Danial, B. Keith, C. B. Thompson, and N. S. Chandel Loss of Mcl-1 Protein and Inhibition of Electron Transport Chain Together Induce Anoxic Cell Death Mol. Cell. Biol., February 15, 2007; 27(4): 1222 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Dzhagalov, A. St. John, and Y.-W. He The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages Blood, February 15, 2007; 109(4): 1620 - 1626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Rosato, J. A. Almenara, S. S. Kolla, S. C. Maggio, S. Coe, M. S. Gimenez, P. Dent, and S. Grant Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions Mol. Cancer Ther., February 1, 2007; 6(2): 692 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chen, Y. Dai, H. Harada, P. Dent, and S. Grant Mcl-1 Down-regulation Potentiates ABT-737 Lethality by Cooperatively Inducing Bak Activation and Bax Translocation Cancer Res., January 15, 2007; 67(2): 782 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Taylor, D. Quilty, L. Banadyga, and M. Barry The Vaccinia Virus Protein F1L Interacts with Bim and Inhibits Activation of the Pro-apoptotic Protein Bax J. Biol. Chem., December 22, 2006; 281(51): 39728 - 39739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Sitailo, S. S. Tibudan, and M. F. Denning The Protein Kinase C{delta} Catalytic Fragment Targets Mcl-1 for Degradation to Trigger Apoptosis J. Biol. Chem., October 6, 2006; 281(40): 29703 - 29710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Degenhardt and E. White A mouse model system to genetically dissect the molecular mechanisms regulating tumorigenesis. Clin. Cancer Res., September 15, 2006; 12(18): 5296 - 5304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Chou, R.-S. Lee, and H.-F. Yang-Yen An Internal EELD Domain Facilitates Mitochondrial Targeting of Mcl-1 via a Tom70-dependent Pathway Mol. Biol. Cell, September 1, 2006; 17(9): 3952 - 3963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pardo, C. Urban, E. M. Galvez, P. G. Ekert, U. Muller, J. Kwon-Chung, M. Lobigs, A. Mullbacher, R. Wallich, C. Borner, et al. The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice J. Cell Biol., August 14, 2006; 174(4): 509 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liang, M. T. Pickering, N.-H. Cho, H. Chang, M. R. Volkert, T. F. Kowalik, and J. U. Jung Deregulation of DNA Damage Signal Transduction by Herpesvirus Latency-Associated M2. J. Virol., June 1, 2006; 80(12): 5862 - 5874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. A. Mongini, J. K. Inman, H. Han, R. J. Fattah, S. B. Abramson, and M. Attur APRIL and BAFF Promote Increased Viability of Replicating Human B2 Cells via Mechanism Involving Cyclooxygenase 2. J. Immunol., June 1, 2006; 176(11): 6736 - 6751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Clohessy, J. Zhuang, J. de Boer, G. Gil-Gomez, and H. J. M. Brady Mcl-1 Interacts with Truncated Bid and Inhibits Its Induction of Cytochrome c Release and Its Role in Receptor-mediated Apoptosis J. Biol. Chem., March 3, 2006; 281(9): 5750 - 5759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Liu, P. Eksarko, V. Temkin, G. K. Haines III, H. Perlman, A. E. Koch, B. Thimmapaya, and R. M. Pope Mcl-1 Is Essential for the Survival of Synovial Fibroblasts in Rheumatoid Arthritis J. Immunol., December 15, 2005; 175(12): 8337 - 8345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Wasilenko, L. Banadyga, D. Bond, and M. Barry The Vaccinia Virus F1L Protein Interacts with the Proapoptotic Protein Bak and Inhibits Bak Activation J. Virol., November 15, 2005; 79(22): 14031 - 14043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. O. Tan, N. Y. Fu, S. K. Sukumaran, S.-L. Chan, J. H. Kang, K. L. Poon, B. S. Chen, and V. C. Yu MAP-1 is a mitochondrial effector of Bax PNAS, October 11, 2005; 102(41): 14623 - 14628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wirth, F. Kuhnel, B. Fleischmann-Mundt, N. Woller, M. Djojosubroto, K. L. Rudolph, M. Manns, L. Zender, and S. Kubicka Telomerase-Dependent Virotherapy Overcomes Resistance of Hepatocellular Carcinomas against Chemotherapy and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand by Elimination of Mcl-1 Cancer Res., August 15, 2005; 65(16): 7393 - 7402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gelinas and E. White BH3-only proteins in control: specificity regulates MCL-1 and BAK-mediated apoptosis Genes & Dev., June 1, 2005; 19(11): 1263 - 1268. [Full Text] [PDF]
|
|
|
|
|
|
S. N. Willis, L. Chen, G. Dewson, A. Wei, E. Naik, J. I. Fletcher, J. M. Adams, and D. C.S. Huang Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins Genes & Dev., June 1, 2005; 19(11): 1294 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Liu, H.-W. Peng, Y.-S. Cheng, H. S. Yuan, and H.-F. Yang-Yen Stabilization and Enhancement of the Antiapoptotic Activity of Mcl-1 by TCTP Mol. Cell. Biol., April 15, 2005; 25(8): 3117 - 3126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Weng, Y. Li, D. Xu, Y. Shi, and H. Tang Specific Cleavage of Mcl-1 by Caspase-3 in Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-induced Apoptosis in Jurkat Leukemia T Cells J. Biol. Chem., March 18, 2005; 280(11): 10491 - 10500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Piret, E. Minet, J.-P. Cosse, N. Ninane, C. Debacq, M. Raes, and C. Michiels Hypoxia-inducible Factor-1-dependent Overexpression of Myeloid Cell Factor-1 Protects Hypoxic Cells against tert-Butyl Hydroperoxide-induced Apoptosis J. Biol. Chem., March 11, 2005; 280(10): 9336 - 9344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Day, L. Chen, S. J. Richardson, P. J. Harrison, D. C. S. Huang, and M. G. Hinds Solution Structure of Prosurvival Mcl-1 and Characterization of Its Binding by Proapoptotic BH3-only Ligands J. Biol. Chem., February 11, 2005; 280(6): 4738 - 4744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Reboredo, R. F. Greaves, and G. Hahn Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication J. Gen. Virol., December 1, 2004; 85(12): 3555 - 3567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Vickers, A. Kasza, I. A. Kurnaz, A. Seifert, L. A. H. Zeef, A. O'Donnell, A. Hayes, and A. D. Sharrocks Ternary Complex Factor-Serum Response Factor Complex-Regulated Gene Activity Is Required for Cellular Proliferation and Inhibition of Apoptotic Cell Death Mol. Cell. Biol., December 1, 2004; 24(23): 10340 - 10351. [Abstract] [Full Text] [PDF]
|
|
