This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuo, M.-L. Articles by Roussel, M. F. Search for Related Content PubMed PubMed Citation Articles by Kuo, M.-L. Articles by Roussel, M. F.

Arf Induces p53-dependent and -independent Antiproliferative Genes^{1 ,2}

Departments of Genetics and Tumor Cell Biology [M-L. K., E. J. D., R. M., W. d. B., C. J. S., M. F. R.], and Biostatistics [D. P., C. C.], the Hartwell Center for Bioinformatics and Biotechnology [D. N.], and Howard Hughes Medical Institute [E. J. D., C. J. S.], St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, and Department of Oncology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639 Japan [T. Y.]

The tumor suppressor p19^Arf (p14^ARF in humans), encoded by the Ink4a/Arf locus, is mutated, deleted, or silenced in many forms of cancer. p19^Arf induces growth arrest by antagonizing the activity of the p53-negative regulator, Mdm2, thereby inducing a p53 transcriptional response. p19^Arf can also inhibit cell cycle progression of mouse embryo fibroblasts lacking Cip1 or lacking both Mdm2 and p53, although in the absence of p53, arrest occurs more slowly. Profiling with high-density oligonucleotide GeneChips and cDNA microarrays was used to interrogate mouse genes, the expression of which was induced or suppressed by a conditionally regulated Arf gene. Cluster analysis of temporal gene expression patterns and validation of the results by RNA analysis identified Arf-responsive genes whose induction was both p53-dependent and -independent. The latter included four members of the B-cell translocation gene family (Btg1, Btg2, Btg3, and Tob1) that were demonstrated to inhibit cell proliferation in primary mouse embryo fibroblasts expressing or lacking functional p53. Together, the results indicate that p19^Arf induces a broad spectrum of proteins that likely act in concert to arrest cell proliferation.

This article has been cited by other articles:

				T. Sebastian and P. F. Johnson RasV12-Mediated Down-regulation of CCAAT/Enhancer Binding Protein {beta} in Immortalized Fibroblasts Requires Loss of p19Arf and Facilitates Bypass of Oncogene-Induced Senescence Cancer Res., March 15, 2009; 69(6): 2588 - 2598. [Abstract] [Full Text] [PDF]

				O. Ayrault, F. Zindy, J. Rehg, C. J. Sherr, and M. F. Roussel Two Tumor Suppressors, p27Kip1 and Patched-1, Collaborate to Prevent Medulloblastoma Mol. Cancer Res., January 1, 2009; 7(1): 33 - 40. [Abstract] [Full Text] [PDF]

				P. Blancafort, M. P. Tschan, S. Bergquist, D. Guthy, A. Brachat, D. A. Sheeter, B. E. Torbett, D. Erdmann, and C. F. Barbas III Modulation of drug resistance by artificial transcription factors Mol. Cancer Ther., March 1, 2008; 7(3): 688 - 697. [Abstract] [Full Text] [PDF]

				J. D. Thornton, D. J. Swanson, M. N. Mary, D. Pei, A. C. Martin, S. Pounds, D. Goldowitz, and S. X. Skapek Persistent Hyperplastic Primary Vitreous Due to Somatic Mosaic Deletion of the Arf Tumor Suppressor Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 491 - 499. [Abstract] [Full Text] [PDF]

				J. D. Wu, K. Haugk, I. Coleman, L. Woodke, R. Vessella, P. Nelson, R. B. Montgomery, D. L. Ludwig, and S. R. Plymate Combined In vivo Effect of A12, a Type 1 Insulin-Like Growth Factor Receptor Antibody, and Docetaxel against Prostate Cancer Tumors. Clin. Cancer Res., October 15, 2006; 12(20): 6153 - 6160. [Abstract] [Full Text] [PDF]

				M. Zeini, P. G. Traves, R. Lopez-Fontal, C. Pantoja, A. Matheu, M. Serrano, L. Bosca, and S. Hortelano Specific Contribution of p19ARF to Nitric Oxide-Dependent Apoptosis. J. Immunol., September 1, 2006; 177(5): 3327 - 3336. [Abstract] [Full Text] [PDF]

				E. Colombo, P. Martinelli, R. Zamponi, D. C. Shing, P. Bonetti, L. Luzi, S. Volorio, L. Bernard, G. Pruneri, M. Alcalay, et al. Delocalization and Destabilization of the Arf Tumor Suppressor by the Leukemia-Associated NPM Mutant. Cancer Res., March 15, 2006; 66(6): 3044 - 3050. [Abstract] [Full Text] [PDF]

				Z. Rahmani APRO4 negatively regulates Src tyrosine kinase activity in PC12 cells J. Cell Sci., February 15, 2006; 119(4): 646 - 658. [Abstract] [Full Text] [PDF]

				C. Carella, M. Potter, J. Bonten, J. E. Rehg, G. Neale, and G. C. Grosveld The ETS factor TEL2 is a hematopoietic oncoprotein Blood, February 1, 2006; 107(3): 1124 - 1132. [Abstract] [Full Text] [PDF]

				M. Sugimoto, A. Gromley, and C. J. Sherr Hzf, a p53-Responsive Gene, Regulates Maintenance of the G2 Phase Checkpoint Induced by DNA Damage Mol. Cell. Biol., January 15, 2006; 26(2): 502 - 512. [Abstract] [Full Text] [PDF]

				A. D. Boiko, S. Porteous, O. V. Razorenova, V. I. Krivokrysenko, B. R. Williams, and A. V. Gudkov A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation Genes & Dev., January 15, 2006; 20(2): 236 - 252. [Abstract] [Full Text] [PDF]

				A. Datta, J. Sen, J. Hagen, C. K. Korgaonkar, M. Caffrey, D. E. Quelle, D. E. Hughes, T. J. Ackerson, R. H. Costa, and P. Raychaudhuri ARF Directly Binds DP1: Interaction with DP1 Coincides with the G1 Arrest Function of ARF Mol. Cell. Biol., September 15, 2005; 25(18): 8024 - 8036. [Abstract] [Full Text] [PDF]

				K. Tago, S. Chiocca, and C. J. Sherr Sumoylation induced by the Arf tumor suppressor: A p53-independent function PNAS, May 24, 2005; 102(21): 7689 - 7694. [Abstract] [Full Text] [PDF]

				G. Normand, P. G. Hemmati, B. Verdoodt, C. von Haefen, J. Wendt, D. Guner, E. May, B. Dorken, and P. T. Daniel p14ARF Induces G2 Cell Cycle Arrest in p53- and p21-deficient Cells by Down-regulating p34cdc2 Kinase Activity J. Biol. Chem., February 25, 2005; 280(8): 7118 - 7130. [Abstract] [Full Text] [PDF]

				R. Sreeramaneni, A. Chaudhry, M. McMahon, C. J. Sherr, and K. Inoue Ras-Raf-Arf Signaling Critically Depends on the Dmp1 Transcription Factor Mol. Cell. Biol., January 1, 2005; 25(1): 220 - 232. [Abstract] [Full Text] [PDF]

				Y. L. Woods, D. P. Xirodimas, A. R. Prescott, A. Sparks, D. P. Lane, and M. K. Saville p14 Arf Promotes Small Ubiquitin-like Modifier Conjugation of Werners Helicase J. Biol. Chem., November 26, 2004; 279(48): 50157 - 50166. [Abstract] [Full Text] [PDF]

				M.-L. Kuo, W. den Besten, D. Bertwistle, M. F. Roussel, and C. J. Sherr N-terminal polyubiquitination and degradation of the Arf tumor suppressor Genes & Dev., August 1, 2004; 18(15): 1862 - 1874. [Abstract] [Full Text] [PDF]

				M. D'Amico, K. Wu, M. Fu, M. Rao, C. Albanese, R. G. Russell, H. Lian, D. Bregman, M. A. White, and R. G. Pestell The Inhibitor of Cyclin-Dependent Kinase 4a/Alternative Reading Frame (INK4a/ARF) Locus Encoded Proteins p16INK4a and p19ARF Repress Cyclin D1 Transcription through Distinct cis Elements Cancer Res., June 15, 2004; 64(12): 4122 - 4130. [Abstract] [Full Text] [PDF]

				B. Calabretta and D. Perrotti The biology of CML blast crisis Blood, June 1, 2004; 103(11): 4010 - 4022. [Abstract] [Full Text] [PDF]

				S. Roy, S. Khanna, W. A. Wallace, J. Lappalainen, C. Rink, A. J. Cardounel, J. L. Zweier, and C. K. Sen Characterization of Perceived Hyperoxia in Isolated Primary Cardiac Fibroblasts and in the Reoxygenated Heart J. Biol. Chem., November 21, 2003; 278(47): 47129 - 47135. [Abstract] [Full Text] [PDF]

				M. P. Tschan, K. M. Fischer, V. S. Fung, F. Pirnia, M. M. Borner, M. F. Fey, A. Tobler, and B. E. Torbett Alternative Splicing of the Human Cyclin D-binding Myb-like Protein (hDMP1) Yields a Truncated Protein Isoform That Alters Macrophage Differentiation Patterns J. Biol. Chem., October 31, 2003; 278(44): 42750 - 42760. [Abstract] [Full Text] [PDF]