JBC Advanced Glycation Endproducts

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M003270200 on September 7, 2000

J. Biol. Chem., Vol. 275, Issue 49, 38319-38328, December 8, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/49/38319    most recent
M003270200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vujcic, S.
Right arrow Articles by Porter, C. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vujcic, S.
Right arrow Articles by Porter, C. W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Effects of Conditional Overexpression of Spermidine/Spermine N1-Acetyltransferase on Polyamine Pool Dynamics, Cell Growth, and Sensitivity to Polyamine Analogs*

Slavoljub VujcicDagger , Maria HalmekytöDagger §, Paula Diegelman, Gregory Gan, Debora L. Kramer, Juhani Jänne§, and Carl W. Porter

From the Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263

Acetylation of polyamines by spermidine/spermine N1-acetyltransferase (SSAT) has been implicated in their degradation and/or export out of the cell. The relationship of SSAT to polyamine pool dynamics and cell growth is not yet clearly understood. MCF-7 human breast carcinoma cells were transfected with tetracycline-regulated (Tet-off) SSAT human cDNA or murine gene. Doxycycline removal for >2 days caused a ~20-fold increase in SSAT RNA and a ~10-fold increase in enzyme activity. After 4 days, intracellular putrescine and spermidine pools were markedly lowered, and cell growth was inhibited. Growth inhibition could not be prevented with exogenous polyamines due to a previously unrecognized ability of SSAT to rapidly acetylate influxing polyamines and thereby prevent restoration of the endogenous pools. Instead, cells accumulated high levels of N1-acetylspermidine, N1-acetylspermine, and N1,N12-diacetylspermine, a metabolite not previously reported in mammalian cells. Doxycycline deprivation before treatment with N1,N11-diethylnorspermine markedly increased analog induction of SSAT mRNA and activity and enhanced growth sensitivity to the analog by ~100-fold. Overall, the findings demonstrate that conditional overexpression of SSAT lowers polyamine pools, inhibits cell growth, and markedly enhances growth sensitivity to certain analogs. The enzyme also plays a remarkably efficient role in maintaining polyamine pool homeostasis during challenges with exogenous polyamines.

* This work was supported in part by National Institutes of Health (NCI) Grants CA-76428 (to C. W. P. and J. J.) and CA-22153 (to C. W. P.) and by Roswell Park Cancer Institute Core Grant CA-16056, by the Academy of Finland, by the Human Frontier Science Program, and by Maud Kuistila's Memorial Foundation (to M. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Shared first authorship.

§ Current address: A. I. Virtanen Institute, University of Kuopio, FIN-70211 Kuopio, Finland.

To whom correspondence and requests for reprints should be addressed: Grace Cancer Drug Center, Roswell Park Cancer Institute, Elm and Carlton Sts., Buffalo, NY 14263. Tel.: 716-845-3002; Fax: 716-845-8857; E-mail: carl.porter@roswellpark.org.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. E. Pegg
Spermidine/spermine-N1-acetyltransferase: a key metabolic regulator
Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E995 - E1010.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. W. deHart, T. Jin, D. E. McCloskey, A. E. Pegg, and D. Sheppard
The {alpha}9{beta}1 integrin enhances cell migration by polyamine-mediated modulation of an inward-rectifier potassium channel
PNAS, May 20, 2008; 105(20): 7188 - 7193.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. L. Kramer, P. Diegelman, J. Jell, S. Vujcic, S. Merali, and C. W. Porter
Polyamine Acetylation Modulates Polyamine Metabolic Flux, a Prelude to Broader Metabolic Consequences
J. Biol. Chem., February 15, 2008; 283(7): 4241 - 4251.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
F. Wu, D. Grossenbacher, and H. Gehring
New transition state-based inhibitor for human ornithine decarboxylase inhibits growth of tumor cells
Mol. Cancer Ther., June 1, 2007; 6(6): 1831 - 1839.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Jell, S. Merali, M. L. Hensen, R. Mazurchuk, J. A. Spernyak, P. Diegelman, N. D. Kisiel, C. Barrero, K. K. Deeb, L. Alhonen, et al.
Genetically Altered Expression of Spermidine/Spermine N1-Acetyltransferase Affects Fat Metabolism in Mice via Acetyl-CoA
J. Biol. Chem., March 16, 2007; 282(11): 8404 - 8413.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
K. Zahedi, J. J. Bissler, Z. Wang, A. Josyula, L. Lu, P. Diegelman, N. Kisiel, C. W. Porter, and M. Soleimani
Spermidine/spermine N1-acetyltransferase overexpression in kidney epithelial cells disrupts polyamine homeostasis, leads to DNA damage, and causes G2 arrest
Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1204 - C1215.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Babbar, A. Hacker, Y. Huang, and R. A. Casero Jr.
Tumor Necrosis Factor {alpha} Induces Spermidine/Spermine N1-Acetyltransferase through Nuclear Factor {kappa}Bin Non-small Cell Lung Cancer Cells
J. Biol. Chem., August 25, 2006; 281(34): 24182 - 24192.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
M. Kawakita and K. Hiramatsu
Diacetylated derivatives of spermine and spermidine as novel promising tumor markers.
J. Biochem., March 1, 2006; 139(3): 315 - 322.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
Y. Wang and R. A. Casero Jr.
Mammalian Polyamine Catabolism: A Therapeutic Target, a Pathological Problem, or Both?
J. Biochem., January 1, 2006; 139(1): 17 - 25.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
G. Marverti, M. G. Monti, A. E. Pegg, D. E. McCloskey, S. Bettuzzi, A. Ligabue, A. Caporali, D. D'Arca, and M. S. Moruzzi
Spermidine/spermine N1-acetyltransferase transient overexpression restores sensitivity of resistant human ovarian cancer cells to N1,N12-bis(ethyl)spermine and to cisplatin
Carcinogenesis, October 1, 2005; 26(10): 1677 - 1686.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. M. Tucker, J. T. Murphy, N. Kisiel, P. Diegelman, K. W. Barbour, C. Davis, M. Medda, L. Alhonen, J. Janne, D. L. Kramer, et al.
Potent Modulation of Intestinal Tumorigenesis in Apcmin/+ Mice by the Polyamine Catabolic Enzyme Spermidine/Spermine N1-acetyltransferase
Cancer Res., June 15, 2005; 65(12): 5390 - 5398.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
N. Martinez, M. Sanchez-Beato, A. Carnero, V. Moneo, J. C. Tercero, I. Fernandez, M. Navarrete, J. Jimeno, and M. A. Piris
Transcriptional signature of Ecteinascidin 743 (Yondelis, Trabectedin) in human sarcoma cells explanted from chemo-naive patients
Mol. Cancer Ther., May 1, 2005; 4(5): 814 - 823.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Hiramatsu, K. Takahashi, T. Yamaguchi, H. Matsumoto, H. Miyamoto, S. Tanaka, C. Tanaka, Y. Tamamori, M. Imajo, M. Kawaguchi, et al.
N1,N12-Diacetylspermine as a Sensitive and Specific Novel Marker for Early- and Late-Stage Colorectal and Breast Cancers
Clin. Cancer Res., April 15, 2005; 11(8): 2986 - 2990.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Kee, B. A. Foster, S. Merali, D. L. Kramer, M. L. Hensen, P. Diegelman, N. Kisiel, S. Vujcic, R. V. Mazurchuk, and C. W. Porter
Activated Polyamine Catabolism Depletes Acetyl-CoA Pools and Suppresses Prostate Tumor Growth in TRAMP Mice
J. Biol. Chem., September 17, 2004; 279(38): 40076 - 40083.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. Hector, C. W. Porter, D. L. Kramer, K. Clark, J. Prey, N. Kisiel, P. Diegelman, Y. Chen, and L. Pendyala
Polyamine catabolism in platinum drug action: Interactions between oxaliplatin and the polyamine analogue N1,N11-diethylnorspermine at the level of spermidine/spermine N1-acetyltransferase
Mol. Cancer Ther., July 1, 2004; 3(7): 813 - 822.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Kee, S. Vujcic, S. Merali, P. Diegelman, N. Kisiel, C. T. Powell, D. L. Kramer, and C. W. Porter
Metabolic and Antiproliferative Consequences of Activated Polyamine Catabolism in LNCaP Prostate Carcinoma Cells
J. Biol. Chem., June 25, 2004; 279(26): 27050 - 27058.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
Y. Huang, J. C. Keen, E. Hager, R. Smith, A. Hacker, B. Frydman, A. L. Valasinas, V. K. Reddy, L. J. Marton, R. A. Casero Jr., et al.
Regulation of Polyamine Analogue Cytotoxicity by c-Jun in Human MDA-MB-435 Cancer Cells
Mol. Cancer Res., February 1, 2004; 2(2): 81 - 88.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. L. Subhi, P. Diegelman, C. W. Porter, B. Tang, Z. J. Lu, G. D. Markham, and W. D. Kruger
Methylthioadenosine Phosphorylase Regulates Ornithine Decarboxylase by Production of Downstream Metabolites
J. Biol. Chem., December 12, 2003; 278(50): 49868 - 49873.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Babbar, N. A. Ignatenko, R. A. Casero Jr., and E. W. Gerner
Cyclooxygenase-independent Induction of Apoptosis by Sulindac Sulfone Is Mediated by Polyamines in Colon Cancer
J. Biol. Chem., November 28, 2003; 278(48): 47762 - 47775.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Chen, D. L. Kramer, J. Jell, S. Vujcic, and C. W. Porter
Small Interfering RNA Suppression of Polyamine Analog-Induced Spermidine/Spermine N1-Acetyltransferase
Mol. Pharmacol., November 1, 2003; 64(5): 1153 - 1159.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
F. Wolter, L. Turchanowa, and J. Stein
Resveratrol-induced modification of polyamine metabolism is accompanied by induction of c-Fos
Carcinogenesis, March 1, 2003; 24(3): 469 - 474.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. A. Christopher, P. Diegelman, C. W. Porter, and W. D. Kruger
Methylthioadenosine Phosphorylase, a Gene Frequently Codeleted with p16cdkN2a/ARF, Acts as a Tumor Suppressor in a Breast Cancer Cell Line
Cancer Res., November 15, 2002; 62(22): 6639 - 6644.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Niiranen, M. Pietila, T. J. Pirttila, A. Jarvinen, M. Halmekyto, V.-P. Korhonen, T. A. Keinanen, L. Alhonen, and J. Janne
Targeted Disruption of Spermidine/Spermine N1-Acetyltransferase Gene in Mouse Embryonic Stem Cells. EFFECTS ON POLYAMINE HOMEOSTASIS AND SENSITIVITY TO POLYAMINE ANALOGUES
J. Biol. Chem., July 5, 2002; 277(28): 25323 - 25328.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. H. Min, R. C. M. Simmen, L. Alhonen, M. Halmekyto, C. W. Porter, J. Janne, and F. A. Simmen
Altered Levels of Growth-related and Novel Gene Transcripts in Reproductive and Other Tissues of Female Mice Overexpressing Spermidine/Spermine N1-Acetyltransferase (SSAT)
J. Biol. Chem., January 25, 2002; 277(5): 3647 - 3657.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Chen, D. L. Kramer, P. Diegelman, S. Vujcic, and C. W. Porter
Apoptotic Signaling in Polyamine Analogue-treated SK-MEL-28 Human Melanoma Cells
Cancer Res., September 1, 2001; 61(17): 6437 - 6444.
[Abstract] [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 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.