|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 274, Issue 50, 35991-35998, December 10, 1999
From the Department of Biochemistry and Molecular Biology,
Louisiana State University Medical Center,
Shreveport, Louisiana 71130-3932
Ribonucleotide reductase synthesizes dNDPs, a
specific and limiting step in DNA synthesis, and can participate in
neoplastic transformation when overexpressed. The small subunit
(ribonucleotide reductase 2 (RNR2)) was cloned as a major product in a
subtraction library from eukaryotic initiation factor 4E
(eIF4E)-transformed cells (Chinese hamster ovary-4E (CHO-4E)). CHO-4E
cells have 20-40-fold elevated RNR2 protein, reflecting an increased
distribution of RNR2 mRNA to the heavy polysomes.
CHO-4E cells display an altered cell cycle with shortened S phase,
similar to cells selected for RNR2 overexpression with
hydroxyurea. The function of ribonucleotide reductase as a checkpoint
component of S progression was studied in yeast in which elevated eIF4E
rescued S-arrested rnr2-68ts cells, by
increasing recruitment of its mRNA to polysomes. Crosses between
rnr2-68ts and mutant eIF4E
(cdc33-1ts) engendered conditional synthetic
lethality, with extreme sensitivity to hydroxyurea and the microtubule
depolymerizing agent, benomyl. The double mutant (cdc33-1
rnr2-68) also identified a unique terminal phenotype, arrested
with small bud and a randomly distributed single nucleus, which is
distinct from those of both parental single mutants. This phenotype
defines eIF4E and RNR2 as determinants in an important cell cycle
checkpoint, in early/mid-S phase. These results also provide a link
between protein and DNA synthesis and provide an explanation for cell
cycle alterations induced by elevated eIF4E.
Translational Regulation of Ribonucleotide Reductase by
Eukaryotic Initiation Factor 4E Links Protein Synthesis to the Control
of DNA Replication*
§,
*
This work was supported by National Science Foundation Grant
MCB9513756 and National Institutes of Health Grant CA69148.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.
Present address: Dept. of Molecular Medicine, Beth Israel
Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave.,
Boston, MA 02215.
§
These authors contributed equally to this paper.
¶
To whom correspondence should be addressed: Dept. of
Biochemistry and Molecular Biology, Louisiana State University Medical Center, 1501 Kings Highway, Shreveport, LA 71130-3932. Tel.:
318-675-5668; Fax: 318-675-5180; E-mail: adeben@lsumc.edu.
Copyright © 1999 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:
|
|
 |
|
  H. Okumura, S. Natsugoe, N. Yokomakura, Y. Kita, M. Matsumoto, Y. Uchikado, T. Setoyama, T. Owaki, S. Ishigami, and T. Aikou Expression of p53R2 Is Related to Prognosis in Patients with Esophageal Squamous Cell Carcinoma. Clin. Cancer Res., June 15, 2006; 12(12): 3740 - 3745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhang, X. An, K. Yang, D. L. Perlstein, L. Hicks, N. Kelleher, J. Stubbe, and M. Huang Nuclear localization of the Saccharomyces cerevisiae ribonucleotide reductase small subunit requires a karyopherin and a WD40 repeat protein PNAS, January 31, 2006; 103(5): 1422 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. CHAN, S. N. KHAN, I. HARVEY, W. MERRICK, and J. PELLETIER Eukaryotic protein synthesis inhibitors identified by comparison of cytotoxicity profiles RNA, March 1, 2004; 10(3): 528 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ju, C. Huang, S. A. Minskoff, J. E. Mayotte, B. E. Taillon, and J. F. Simons Simultaneous gene expression analysis of steady-state and actively translated mRNA populations from osteosarcoma MG-63 cells in response to IL-1{alpha} via an open expression analysis platform Nucleic Acids Res., September 1, 2003; 31(17): 5157 - 5166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Arai, O. Yokosuka, T. Chiba, F. Imazeki, M. Kato, J. Hashida, Y. Ueda, S. Sugano, K. Hashimoto, H. Saisho, et al. Gene Expression Profiling Reveals the Mechanism and Pathophysiology of Mouse Liver Regeneration J. Biol. Chem., August 8, 2003; 278(32): 29813 - 29818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. B. Borden Pondering the Promyelocytic Leukemia Protein (PML) Puzzle: Possible Functions for PML Nuclear Bodies Mol. Cell. Biol., August 1, 2002; 22(15): 5259 - 5269. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Smeds, R. Kumar, and K. Hemminki Polymorphic insertion of additional repeat within an area of direct 8 bp tandem repeats in the 5'-untranslated region of the p53R2 gene and cancer risk Mutagenesis, November 1, 2001; 16(6): 547 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Anthony, Q. Zong, and A. De Benedetti Overexpression of eIF4E in Saccharomyces cerevisiae Causes Slow Growth and Decreased alpha -Factor Response through Alterations in CLN3 Expression J. Biol. Chem., October 19, 2001; 276(43): 39645 - 39652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ge, D. L. Perlstein, H.-H. Nguyen, G. Bar, R. G. Griffin, and J. Stubbe Why multiple small subunits (Y2 and Y4) for yeast ribonucleotide reductase? Toward understanding the role of Y4 PNAS, August 28, 2001; 98(18): 10067 - 10072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Berkel, E. A. Turbat-Herrera, R. Shi, and A. de Benedetti Expression of the Translation Initiation Factor eIF4E in the Polyp-Cancer Sequence in the Colon Cancer Epidemiol. Biomarkers Prev., June 1, 2001; 10(6): 663 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Liu, B. S. Nefsky, and N. C. Walworth The Ded1 DEAD Box Helicase Interacts with Chk1 and Cdc2 J. Biol. Chem., January 18, 2002; 277(4): 2637 - 2643. [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 |