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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				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

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

				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]