The Journal of Cell Biology, Vol 134, 193-204, Copyright © 1996 by The Rockefeller University Press

ARTICLES

Interference with p53 protein inhibits hematopoietic and muscle differentiation

S Soddu, G Blandino, R Scardigli, S Coen, A Marchetti, MG Rizzo, G Bossi, L Cimino, M Crescenzi and A Sacchi
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute--Centro Ricerca Sperimentale, Rome, Italy.

The involvement of p53 protein in cell differentiation has been recently suggested by some observations made with tumor cells and the correlation found between differentiation and increased levels of p53. However, the effect of p53 on differentiation is in apparent contrast with the normal development of p53-null mice. To test directly whether p53 has a function in cell differentiation, we interfered with the endogenous wt-p53 protein of nontransformed cells of two different murine histotypes: 32D myeloid progenitors, and C2C12 myoblasts. A drastic inhibition of terminal differentiation into granulocytes or myotubes, respectively, was observed upon expression of dominant- negative p53 proteins. This inhibition did not alter the cell cycle withdrawal typical of terminal differentiation, nor p21(WAF1/CIP1) upregulation, indicating that interference with endogenous p53 directly affects cell differentiation, independently of the p53 activity on the cell cycle. We also found that the endogenous wt-p53 protein of C2C12 cells becomes transcriptionally active during myogenesis, and this activity is inhibited by p53 dominant-negative expression. Moreover, we found that p53 DNA-binding and transcriptional activities are both required to induce differentiation in p53-negative K562 cells. Taken together, these data strongly indicate that p53 is a regulator of cell differentiation and it exerts this role, at least in part, through its transcriptional activity.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Fuhrken, P. G., Apostolidis, P. A., Lindsey, S., Miller, W. M., Papoutsakis, E. T. (2008). Tumor Suppressor Protein p53 Regulates Megakaryocytic Polyploidization and Apoptosis. J. Biol. Chem. 283: 15589-15600 [Abstract] [Full Text]  
• Besteman, E. G., Zimmerman, K. L., Huckle, W. R., Prater, M. R., Gogal, R. M. Jr., Holladay, S. D. (2007). 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) or Diethylstilbestrol (DES) Cause Similar Hematopoietic Hypocellularity and Hepatocellular Changes in Murine Fetal Liver, but Differentially Affect Gene Expression. Toxicol Pathol 35: 786-792 [Abstract] [Full Text]  
• Schwarzkopf, M., Coletti, D., Sassoon, D., Marazzi, G. (2006). Muscle cachexia is regulated by a p53-PW1/Peg3-dependent pathway. Genes Dev. 20: 3440-3452 [Abstract] [Full Text]  
• Kathrein, K. L., Lorenz, R., Innes, A. M., Griffiths, E., Winandy, S. (2005). Ikaros Induces Quiescence and T-Cell Differentiation in a Leukemia Cell Line. Mol. Cell. Biol. 25: 1645-1654 [Abstract] [Full Text]  
• Hawke, T. J., Meeson, A. P., Jiang, N., Graham, S., Hutcheson, K., DiMaio, J. M., Garry, D. J. (2003). p21 is essential for normal myogenic progenitor cell function in regenerating skeletal muscle. Am. J. Physiol. Cell Physiol. 285: C1019-C1027 [Abstract] [Full Text]  
• Saifudeen, Z., Marks, J., Du, H., El-Dahr, S. S. (2002). Spatial repression of PCNA by p53 during kidney development. Am. J. Physiol. Renal Physiol. 283: F727-F733 [Abstract] [Full Text]  
• Sciacchitano, S., Orecchio, A., Lavra, L., Misiti, S., Giacchini, A., Zani, M., Danese, D., Gurtner, A., Soddu, S., Di Mario, U., Andreoli, M. (2002). Cloning of the Mouse Insulin Receptor Substrate-3 (mIRS-3) Promoter, and Its Regulation by p53. Mol. Endocrinol. 16: 1577-1589 [Abstract] [Full Text]  
• Morena, A., Riccioni, S., Marchetti, A., Polcini, A. T., Mercurio, A. M., Blandino, G., Sacchi, A., Falcioni, R. (2002). Expression of the beta 4 integrin subunit induces monocytic differentiation of 32D/v-Abl cells. Blood 100: 96-106 [Abstract] [Full Text]  
• Hall, P A, Woodman, A C, Campbell, S J, Shepherd, N A (2001). Expression of the p53 homologue p63{alpha} and {Delta}Np63{alpha} in the neoplastic sequence of Barrett's oesophagus: correlation with morphology and p53 protein. Gut 49: 618-623 [Abstract] [Full Text]  
• Gaitonde, S. V., Qi, W., Falsey, R. R., Sidell, N., Martinez, J. D. (2001). Morphologic Conversion of a Neuroblastoma-derived Cell Line by E6-mediated p53 Degradation. Cell Growth Differ. 12: 19-27 [Abstract] [Full Text]  
• Porrello, A., Cerone, M. A., Coen, S., Gurtner, A., Fontemaggi, G., Cimino, L., Piaggio, G., Sacchi, A., Soddu, S. (2000). P53 Regulates Myogenesis by Triggering the Differentiation Activity of Prb. JCB 151: 1295-1304 [Abstract] [Full Text]  
• Chylicki, K., Ehinger, M., Svedberg, H., Gullberg, U. (2000). Characterization of the Molecular Mechanisms for p53-mediated Differentiation. Cell Growth Differ. 11: 561-571 [Abstract] [Full Text]  
• Chylicki, K., Ehinger, M., Svedberg, H., Bergh, G., Olsson, I., Gullberg, U. (2000). p53-mediated Differentiation of the Erythroleukemia Cell Line K562. Cell Growth Differ. 11: 315-324 [Abstract] [Full Text]  
• Hall, P. A., Campbell, S. J., O'neill, M., Royston, D. J., Nylander, K., Carey, F. A., Kernohan, N. M. (2000). Expression of the p53 homologue p63{alpha} and {Delta}Np63{alpha} in normal and neoplasticcells. Carcinogenesis 21: 153-160 [Abstract] [Full Text]  
• Bachelder, R. E., Marchetti, A., Falcioni, R., Soddu, S., Mercurio, A. M. (1999). Activation of p53 Function in Carcinoma Cells by the alpha 6beta 4 Integrin. J. Biol. Chem. 274: 20733-20737 [Abstract] [Full Text]  
• Wadhwa, R., Sugihara, T., Yoshida, A., Duncan, E. L., Hardeman, E. C., Nomura, H., Reddel, R. R., Kaul, S. C. (1999). Cloning and Characterization of a Novel Gene, striamin, That Interacts with the Tumor Suppressor Protein p53. J. Biol. Chem. 274: 14948-14955 [Abstract] [Full Text]  
• Ruiz-Lozano, P., Hixon, M. L., Wagner, M. W., Flores, A. I., Ikawa, S., Baldwin, A. S. Jr., Chien, K. R., Gualberto, A. (1999). p53 Is a Transcriptional Activator of the Muscle-specific Phosphoglycerate Mutase Gene and Contributesin Vivo to the Control of Its Cardiac Expression. Cell Growth Differ. 10: 295-306 [Abstract] [Full Text]  
• Lee, K. C., Crowe, A. J., Barton, M. C. (1999). p53-Mediated Repression of Alpha-Fetoprotein Gene Expression by Specific DNA Binding. Mol. Cell. Biol. 19: 1279-1288 [Abstract] [Full Text]  
• Gottifredi, V, Peschiaroli, A, Fimia, G., Maione, R (1999). p53-independent apoptosis induced by muscle differentiation stimuli in polyomavirus large T-expressing myoblasts. J. Cell Sci. 112: 2397-2407 [Abstract]  
• Hixon, M. L., Flores, A. I., Wagner, M. W., Gualberto, A. (1998). Ectopic Expression of cdc2/cdc28 Kinase Subunit Homo sapiens 1 Uncouples Cyclin B Metabolism from the Mitotic Spindle Cell Cycle Checkpoint. Mol. Cell. Biol. 18: 6224-6237 [Abstract] [Full Text]  
• Wechsler-Reya, R. J., Elliott, K. J., Prendergast, G. C. (1998). A Role for the Putative Tumor Suppressor Bin1 in Muscle Cell Differentiation. Mol. Cell. Biol. 18: 566-575 [Abstract] [Full Text]  
• Moll, U.M., Schramm, L.M. (1998). p53--An Acrobat in Tumorigenesis. CROBM 9: 23-37 [Abstract] [Full Text]  
• Narayan, S., Jaiswal, A. S. (1997). Activation of Adenomatous Polyposis Coli (APC) Gene Expression by the DNA-alkylating Agent N-MethylN'-nitro-N-nitrosoguanidine Requires p53. J. Biol. Chem. 272: 30619-30622 [Abstract] [Full Text]  
• Manni, I., Mazzaro, G., Gurtner, A., Mantovani, R., Haugwitz, U., Krause, K., Engeland, K., Sacchi, A., Soddu, S., Piaggio, G. (2001). NF-Y Mediates the Transcriptional Inhibition of the cyclin B1, cyclin B2, and cdc25C Promoters upon Induced G2 Arrest. J. Biol. Chem. 276: 5570-5576 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents