| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, August 31, 1995, and in revised form, June 15, 1996)
From the Oncology and Immunology Research Division, Wyeth-Ayerst
Research, Pearl River, New York 10965
Topoisomerase II is an essential enzyme for
proliferation of eukaryotic cells. It is also a target for many
antineoplastic drugs that promote stabilization of covalent complexes
between topoisomerase II and DNA. Topoisomerase II and protein kinases
both catalyze the transfer of phosphoester bonds from nucleotides to
proteins. This similarity suggests that inhibitors may affect both
classes of enzymes. In the present study, we have examined the
mechanism of topoisomerase II inhibition by three different classes of
protein kinase inhibitors. We report that staurosporine inhibited the
catalytic activity of topoisomerase II by blocking the transfer of
phosphodiester bonds from DNA to the active tyrosine site, a mechanism
of inhibition not previously reported for this enzyme. In contrast,
other kinase inhibitors, such as methyl 2,5-dihydroxycinnamate, most
likely inactivated topoisomerase II by alkylation of essential amino
acids, whereas the mechanism of inhibition of bis-indolylmaleimide
possibly involved a direct interaction with DNA.
Volume 271, Number 42,
Issue of October 18, 1996
pp. 26418-26423
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L. P. Swift, A. Rephaeli, A. Nudelman, D. R. Phillips, and S. M. Cutts Doxorubicin-DNA Adducts Induce a Non-Topoisomerase II-Mediated Form of Cell Death. Cancer Res., May 1, 2006; 66(9): 4863 - 4871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Watson, J. M. McKim, G. L. Cockerell, and J. I. Goodman The Value of DNA Methylation Analysis in Basic, Initial Toxicity Assessments Toxicol. Sci., May 1, 2004; 79(1): 178 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hooiveld, G. Roosendaal, M. Wenting, M. van den Berg, J. Bijlsma, and F. Lafeber Short-Term Exposure of Cartilage to Blood Results in Chondrocyte Apoptosis Am. J. Pathol., March 1, 2003; 162(3): 943 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F. Webb, Y. Yamashita, N. Ayers, S. Evetts, Y. Paulin, M. E. Conley, and E. A. Smith The Transcription Factor Bright Associates with Bruton's Tyrosine Kinase, the Defective Protein in Immunodeficiency Disease J. Immunol., December 15, 2000; 165(12): 6956 - 6965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Marcelli, G. R. Cunningham, M. Walkup, Z. He, L. Sturgis, C. Kagan, R. Mannucci, I. Nicoletti, B. Teng, and L. Denner Signaling Pathway Activated during Apoptosis of the Prostate Cancer Cell Line LNCaP: Overexpression of Caspase-7 as a New Gene Therapy Strategy for Prostate Cancer Cancer Res., January 1, 1999; 59(2): 382 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Fortune and N. Osheroff Merbarone Inhibits the Catalytic Activity of Human Topoisomerase IIalpha by Blocking DNA Cleavage J. Biol. Chem., July 10, 1998; 273(28): 17643 - 17650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kwon, B. S. Shin, and I. K. Chung The p53 Tumor Suppressor Stimulates the Catalytic Activity of Human Topoisomerase IIalpha by Enhancing the Rate of ATP Hydrolysis J. Biol. Chem., June 9, 2000; 275(24): 18503 - 18510. [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 |
