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Cell Growth & Differentiation, Vol 8, Issue 10 1039-1048, Copyright © 1997 by American Association of Cancer Research


ARTICLES

Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination

MK Mateyak, AJ Obaya, S Adachi and JM Sedivy
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.

Rat fibroblast cell lines with targeted disruptions of both c-myc gene copies were constructed. Although c-myc null cells are viable, their growth is significantly impaired. The absence of detectable N-myc or L-myc expression indicates that Myc function is not absolutely essential for cell viability. The c-myc null phenotype is stable and can be reverted by introduction of a c-myc transgene. Exponentially growing c-myc null cells have the same cell size, rRNA, and total protein content as their c-myc +/+ parents, but the rates of RNA and protein accumulation as well as protein degradation are reduced. Both the G1 and G2 phases of the cell cycle are significantly lengthened, whereas the duration of S phase is unaffected. This is the first direct demonstration of a requirement for c-myc in G2. The G0-->S transition is synchronous, but S-phase entry is significantly delayed. The c-myc null cell lines reported here are a new experimental system in which to investigate the importance of putative c-Myc target genes and to identify novel downstream genes involved in cell cycle progression and apoptosis.


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Cancer Res.Home page
S. Silva, A. L. Kovalchuk, J. S. Kim, G. Klein, and S. Janz
BCL2 Accelerates Inflammation-induced BALB/c Plasmacytomas and Promotes Novel Tumors with Coexisting T(12;15) and T(6;15) Translocations
Cancer Res., December 15, 2003; 63(24): 8656 - 8663.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
J. Xiong, S. Fan, Q. Meng, L. Schramm, C. Wang, B. Bouzahza, J. Zhou, B. Zafonte, I. D. Goldberg, B. R. Haddad, et al.
BRCA1 Inhibition of Telomerase Activity in Cultured Cells
Mol. Cell. Biol., December 1, 2003; 23(23): 8668 - 8690.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
S. W. Park and L.-N. Wei
Regulation of c-myc Gene by Nitric Oxide via Inactivating NF-{kappa}B Complex in P19 Mouse Embryonal Carcinoma Cells
J. Biol. Chem., August 8, 2003; 278(32): 29776 - 29782.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
R. Wadhawan, Y.-T. Tseng, J. Stabila, B. McGonnigal, S. Sarkar, and J. Padbury
Regulation of cardiac beta 1-adrenergic receptor transcription during the developmental transition
Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2146 - H2152.
[Abstract] [Full Text] [PDF]


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Genes Dev.Home page
D. L. Levens
Reconstructing MYC
Genes & Dev., May 1, 2003; 17(9): 1071 - 1077.
[Full Text] [PDF]


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Genes Dev.Home page
P. C. Fernandez, S. R. Frank, L. Wang, M. Schroeder, S. Liu, J. Greene, A. Cocito, and B. Amati
Genomic targets of the human c-Myc protein
Genes & Dev., May 1, 2003; 17(9): 1115 - 1129.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
W. Wei, W. A. Jobling, W. Chen, W. C. Hahn, and J. M. Sedivy
Abolition of Cyclin-Dependent Kinase Inhibitor p16Ink4a and p21Cip1/Waf1 Functions Permits Ras-Induced Anchorage-Independent Growth in Telomerase-Immortalized Human Fibroblasts
Mol. Cell. Biol., April 15, 2003; 23(8): 2859 - 2870.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
B. C. O'Connell, A. F. Cheung, C. P. Simkevich, W. Tam, X. Ren, M. K. Mateyak, and J. M. Sedivy
A Large Scale Genetic Analysis of c-Myc-regulated Gene Expression Patterns
J. Biol. Chem., April 4, 2003; 278(14): 12563 - 12573.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
M. A. Nikiforov, N. Popov, I. Kotenko, M. Henriksson, and M. D. Cole
The Mad and Myc Basic Domains Are Functionally Equivalent
J. Biol. Chem., March 28, 2003; 278(13): 11094 - 11099.
[Abstract] [Full Text] [PDF]


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Mol. Biol. CellHome page
C. Schorl and J. M. Sedivy
Loss of Protooncogene c-Myc Function Impedes G1 Phase Progression Both before and after the Restriction Point
Mol. Biol. Cell, March 1, 2003; 14(3): 823 - 835.
[Abstract] [Full Text] [PDF]


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Genes Dev.Home page
F. Morrish, C. Giedt, and D. Hockenbery
c-MYC apoptotic function is mediated by NRF-1 target genes
Genes & Dev., January 15, 2003; 17(2): 240 - 255.
[Abstract] [Full Text] [PDF]


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DevelopmentHome page
A. M. Kenney, M. D. Cole, and D. H. Rowitch
Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors
Development, January 1, 2003; 130(1): 15 - 28.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
A. Hackzell, H. Uramoto, H. Izumi, K. Kohno, and K. Funa
p73 Independent of c-Myc Represses Transcription of Platelet-derived Growth Factor {beta}-Receptor through Interaction with NF-Y
J. Biol. Chem., October 18, 2002; 277(42): 39769 - 39776.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
J. D. Watson, S. K. Oster, M. Shago, F. Khosravi, and L. Z. Penn
Identifying Genes Regulated in a Myc-dependent Manner
J. Biol. Chem., October 4, 2002; 277(40): 36921 - 36930.
[Abstract] [Full Text] [PDF]


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EMBO J.Home page
Y. Shiio, S. Donohoe, E. C. Yi, D. R. Goodlett, R. Aebersold, and R. N. Eisenman
Quantitative proteomic analysis of Myc oncoprotein function
EMBO J., October 1, 2002; 21(19): 5088 - 5096.
[Abstract] [Full Text] [PDF]


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Genes Dev.Home page
T. A. Baudino, C. McKay, H. Pendeville-Samain, J. A. Nilsson, K. H. Maclean, E. L. White, A. C. Davis, J. N. Ihle, and J. L. Cleveland
c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression
Genes & Dev., October 1, 2002; 16(19): 2530 - 2543.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
Z. You, L. V. Madrid, D. Saims, J. Sedivy, and C.-Y. Wang
c-Myc Sensitizes Cells to Tumor Necrosis Factor-mediated Apoptosis by Inhibiting Nuclear Factor {kappa}B Transactivation
J. Biol. Chem., September 27, 2002; 277(39): 36671 - 36677.
[Abstract] [Full Text] [PDF]


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EMBO J.Home page
Y. Cao, E. M. Janssen, A. W. Duncan, A. Altman, D. D. Billadeau, and R. T. Abraham
Pleiotropic defects in TCR signaling in a Vav-1-null Jurkat T-cell line
EMBO J., September 16, 2002; 21(18): 4809 - 4819.
[Abstract] [Full Text] [PDF]


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EMBO J.Home page
B. M. Iritani, J. Delrow, C. Grandori, I. Gomez, M. Klacking, L. S. Carlos, and R. N. Eisenman
Modulation of T-lymphocyte development, growth and cell size by the Myc antagonist and transcriptional repressor Mad1
EMBO J., September 16, 2002; 21(18): 4820 - 4830.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
H. Uramoto, H. Izumi, T. Ise, M. Tada, T. Uchiumi, M. Kuwano, K. Yasumoto, K. Funa, and K. Kohno
p73 Interacts with c-Myc to Regulate Y-box-binding Protein-1 Expression
J. Biol. Chem., August 30, 2002; 277(35): 31694 - 31702.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
A. J. Obaya, I. Kotenko, M. D. Cole, and J. M. Sedivy
The Proto-oncogene c-myc Acts through the Cyclin-dependent Kinase (Cdk) Inhibitor p27Kip1to Facilitate the Activation of Cdk4/6 and Early G1Phase Progression
J. Biol. Chem., August 23, 2002; 277(34): 31263 - 31269.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
M. A. Nikiforov, S. Chandriani, B. O'Connell, O. Petrenko, I. Kotenko, A. Beavis, J. M. Sedivy, and M. D. Cole
A Functional Screen for Myc-Responsive Genes Reveals Serine Hydroxymethyltransferase, a Major Source of the One-Carbon Unit for Cell Metabolism
Mol. Cell. Biol., August 15, 2002; 22(16): 5793 - 5800.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
L. James and R. N. Eisenman
Myc and Mad bHLHZ domains possess identical DNA-binding specificities but only partially overlapping functions in vivo
PNAS, August 6, 2002; 99(16): 10429 - 10434.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
M. A. Nikiforov, S. Chandriani, J. Park, I. Kotenko, D. Matheos, A. Johnsson, S. B. McMahon, and M. D. Cole
TRRAP-Dependent and TRRAP-Independent Transcriptional Activation by Myc Family Oncoproteins
Mol. Cell. Biol., July 15, 2002; 22(14): 5054 - 5063.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
I. Lemm and J. Ross
Regulation of c-myc mRNA Decay by Translational Pausing in a Coding Region Instability Determinant
Mol. Cell. Biol., June 15, 2002; 22(12): 3959 - 3969.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
J. S. Carroll, A. Swarbrick, E. A. Musgrove, and R. L. Sutherland
Mechanisms of Growth Arrest by c-myc Antisense Oligonucleotides in MCF-7 Breast Cancer Cells: Implications for the Antiproliferative Effects of Antiestrogens
Cancer Res., June 1, 2002; 62(11): 3126 - 3131.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
D. R. Wonsey, K. I. Zeller, and C. V. Dang
The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation
PNAS, May 14, 2002; 99(10): 6649 - 6654.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
D. Levens
Disentangling the MYC web
PNAS, April 30, 2002; 99(9): 5757 - 5759.
[Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
A. Menssen and H. Hermeking
Characterization of the c-MYC-regulated transcriptome by SAGE: Identification and analysis of c-MYC target genes
PNAS, April 30, 2002; 99(9): 6274 - 6279.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
Q. Yu, M. He, N. H. Lee, and E. T. Liu
Identification of Myc-mediated Death Response Pathways by Microarray Analysis
J. Biol. Chem., April 12, 2002; 277(15): 13059 - 13066.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
J. Park, M. A. Wood, and M. D. Cole
BAF53 Forms Distinct Nuclear Complexes and Functions as a Critical c-Myc-Interacting Nuclear Cofactor for Oncogenic Transformation
Mol. Cell. Biol., March 1, 2002; 22(5): 1307 - 1316.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
J. E. Prescott, R. C. Osthus, L. A. Lee, B. C. Lewis, H. Shim, J. F. Barrett, Q. Guo, A. L. Hawkins, C. A. Griffin, and C. V. Dang
A Novel c-Myc-responsive Gene, JPO1, Participates in Neoplastic Transformation
J. Biol. Chem., December 21, 2001; 276(51): 48276 - 48284.
[Abstract] [Full Text] [PDF]




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