| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print November 1, 2001
Department of Pharmacology, University of Kentucky College of Medicine, Lexington, KY 40536-0084
Corresponding Author: dmkaetz{at}pop.uky.edu
The PDGF-A promoter is regulated by a number of GC-rich regulatory elements which possess non-B form DNA structures. Screening of a HeLa cDNA expression library with the C-rich strand of a PDGF-A silencer sequence (5’SHS) yielded three cDNA clones encoding NM23-H1, a protein implicated as a suppressor of metastasis in melanoma and breast carcinoma. Recombinant human NM23-H1 cleaved within the 3’-portions of both 5’SHS strands in either single-stranded or duplex forms. In contrast, NM23-H2, known as a transcriptional activator with a DNA-cleavage function, cleaved within the 5’-portions of both strands, revealing that NM23-H1 and NM23-H2 cleave at distinct sites of the 5’SHS and by different mechanisms. NM23-H1 and NM23-H2 also cleaved within the PDGF-A basal promoter region, again exhibiting preferences for cleavage within the 5’- and 3’-portions of the element, respectively. Transient transfection analyses in HepG2 cells revealed that both NM23-H1 and -H2 repressed transcriptional activity driven by the PDGF-A basal promoter (-82 to +8). Activity of the negative regulatory region (-1853 to -883), which contains the 5’SHS, was also inhibited modestly by NM23-H1 and NM23-H2. These studies demonstrate for the first time that NM23-H1 interacts both structurally and functionally with DNA. They also indicate a role for NM23 proteins in repressing transcription of a growth factor oncogene, providing a possible molecular mechanism to explain their metastasis-suppressing effects.
J. Biol. Chem, 10.1074/jbc.M108359200
Submitted on August 29, 2001
Revised on October 23, 2001
Accepted on October 31, 2001
NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the PDGF-A promoter
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Nallamothu, J. A. Woolworth, V. Dammai, and T. Hsu awd, the Homolog of Metastasis Suppressor Gene Nm23, Regulates Drosophila Epithelial Cell Invasion Mol. Cell. Biol., March 15, 2008; 28(6): 1964 - 1973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. K. Yadav, J. K. Abraham, P. Mani, R. Kulshrestha, and S. Chowdhury QuadBase: genome-wide database of G4 DNA occurrence and conservation in human, chimpanzee, mouse and rat promoters and 146 microbes Nucleic Acids Res., January 11, 2008; 36(suppl_1): D381 - D385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Qin, E. M. Rezler, V. Gokhale, D. Sun, and L. H. Hurley Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4 Nucleic Acids Res., December 3, 2007; 35(22): 7698 - 7713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. McAlinden, L. Liang, Y. Mukudai, T. Imamura, and L. J. Sandell Nuclear Protein TIA-1 Regulates COL2A1 Alternative Splicing and Interacts with Precursor mRNA and Genomic DNA J. Biol. Chem., August 17, 2007; 282(33): 24444 - 24454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-A Seong, H. Jung, and H. Ha NM23-H1 Tumor Suppressor Physically Interacts with Serine-Threonine Kinase Receptor-associated Protein, a Transforming Growth Factor-beta (TGF-beta) Receptor-interacting Protein, and Negatively Regulates TGF-beta Signaling J. Biol. Chem., April 20, 2007; 282(16): 12075 - 12096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Rayner, Y.-X. Chen, B. Hibbert, D. White, H. Miller, E. H. Postel, and E. R. O'Brien NM23-H2, an estrogen receptor beta-associated protein, shows diminished expression with progression of atherosclerosis Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R743 - R750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Goswami, J.-H. Yoon, B. M. Abramczyk, G. P. Pfeifer, and E. H. Postel Molecular and Functional Interactions between Escherichia coli Nucleoside-diphosphate Kinase and the Uracil-DNA Glycosylase Ung J. Biol. Chem., October 27, 2006; 281(43): 32131 - 32139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kaul, S. C. Verma, M. Murakami, K. Lan, T. Choudhuri, and E. S. Robertson Epstein-Barr Virus Protein Can Upregulate Cyclo-Oxygenase-2 Expression through Association with the Suppressor of Metastasis Nm23-H1 J. Virol., February 1, 2006; 80(3): 1321 - 1331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Kuppers, K. Lan, J. S. Knight, and E. S. Robertson Regulation of Matrix Metalloproteinase 9 Expression by Epstein-Barr Virus Nuclear Antigen 3C and the Suppressor of Metastasis Nm23-H1 J. Virol., August 1, 2005; 79(15): 9714 - 9724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Boissan, D. Wendum, S. Arnaud-Dabernat, A. Munier, M. Debray, I. Lascu, J.-Y. Daniel, and M.-L. Lacombe Increased Lung Metastasis in Transgenic NM23-Null/SV40 Mice with Hepatocellular Carcinoma J Natl Cancer Inst, June 1, 2005; 97(11): 836 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kumar, A. Verma, A. K. Saini, P. Chopra, P. K. Chakraborti, Y. Singh, and S. Chowdhury Nucleoside diphosphate kinase from Mycobacterium tuberculosis cleaves single strand DNA within the human c-myc promoter in an enzyme-catalyzed reaction Nucleic Acids Res., May 11, 2005; 33(8): 2707 - 2714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ma, J. R. McCorkle, and D. M. Kaetzel The Metastasis Suppressor NM23-H1 Possesses 3'-5' Exonuclease Activity J. Biol. Chem., April 23, 2004; 279(17): 18073 - 18084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Postel and B. M. Abramczyk Escherichia coli nucleoside diphosphate kinase is a uracil-processing DNA repair nuclease PNAS, November 11, 2003; 100(23): 13247 - 13252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Siddiqui-Jain, C. L. Grand, D. J. Bearss, and L. H. Hurley Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription PNAS, September 3, 2002; 99(18): 11593 - 11598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Hartsough, D. K. Morrison, M. Salerno, D. Palmieri, T. Ouatas, M. Mair, J. Patrick, and P. S. Steeg Nm23-H1 Metastasis Suppressor Phosphorylation of Kinase Suppressor of Ras via a Histidine Protein Kinase Pathway J. Biol. Chem., August 23, 2002; 277(35): 32389 - 32399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-N. Fournier, S. Dupe-Manet, D. Bouvard, M.-L. Lacombe, C. Marie, M. R. Block, and C. Albiges-Rizo Integrin Cytoplasmic Domain-associated Protein 1alpha (ICAP-1alpha ) Interacts Directly with the Metastasis Suppressor nm23-H2, and Both Proteins Are Targeted to Newly Formed Cell Adhesion Sites upon Integrin Engagement J. Biol. Chem., May 31, 2002; 277(23): 20895 - 20902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Levit, B. M. Abramczyk, J. B. Stock, and E. H. Postel Interactions between Escherichia coli Nucleoside-diphosphate Kinase and DNA J. Biol. Chem., February 8, 2002; 277(7): 5163 - 5167. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
