Abstract
The P73 gene is transcribed from two promoters, P1 and P2, that direct the expression of multiple transactivation competent (TA) and dominant negative (DN) isoforms. TAp73 transcription factors mediate cell cycle arrest and/or apoptosis in response to DNA damage and are involved in developmental processes. P73 mRNA levels increase and the P1p73 promoter is upregulated during myogenic differentiation of C2C12 skeletal muscle satellite cells. The DNp73 proteins act as trans-repressors of p53- and p73-dependent transcription, and possess both antiapoptotic and pro-proliferative potential. Here, we show that DNp73α is expressed in proliferating C2C12 myoblasts, rapidly accumulates in differentiating myocytes and remains elevated in C2C12 myotubes. By combining transactivation assays and chromatin immunoprecipitation analysis, we could show that the upregulation of the P2p73 promoter during myogenic differentiation is mediated by the coordinated recruitment and activity of MyoD and p53/p73. Abrogation of DNp73 expression by specific siRNA led to a strong potentiation of the spontaneous apoptosis of C2C12 myoblasts induced to differentiate. Finally, unlike TAp73 that contributes to DNA damage-induced apoptosis of myotubes, endogenous DNp73 mediates the relative resistance of differentiated myotubes to DNA damage. Altogether, our findings identify DNp73α as an important target in designing strategies aimed at the potentiation of the regenerative potential of skeletal satellite cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Billon N, Terrinoni A, Jolicoeur C, McCarthy A, Richardson WD, Melino G et al. (2004). Development 131: 1211–1220.
Cerone MA, Marchetti A, Bossi G, Blandino G, Sacchi A, Soddu S . (2000). Cell Death Differ 7: 506–508.
Costanzo A, Merlo P, Pediconi N, Fulco M, Sartorelli V, Cole PA et al. (2002). Mol Cell 9: 175–186.
De Laurenzi V, Raschella G, Barcaroli D, Annicchiarico-Petruzzelli M, Ranalli M, Catani MV et al. (2000a). J Biol Chem 275: 15226–15231.
De Laurenzi V, Rossi A, Terrinoni A, Barcaroli D, Levrero M, Costanzo A et al. (2000b). Biochem Biophys Res Commun 273: 342–346.
Fontemaggi G, Gurtner A, Strano S, Higashi Y, Sacchi A, Piaggio G et al. (2001). Mol Cell Biol 21: 8461–8470.
Fontemaggi G, Kela I, Amariglio N, Rechavi G, Krishnamurthy J, Strano S et al. (2002). J Biol Chem 277: 43359–43368.
Halevy O . (1993). Biochem Biophys Res Commun 192: 714–719.
Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W et al. (2000). Nature 407: 645–648.
Kartasheva NN, Contente A, Lenz-Stoppler C, Roth J, Dobbelstein M . (2002). Oncogene 21: 4715–4727.
Latella L, Lukas J, Simone C, Puri PL, Bartek J . (2004). Mol Cell Biol 24: 6350–6361.
Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G . (2000). J Cell Sci 113: 1661–1670.
Li CY, Zhu J, Wang JY . (2005). J Biol Chem 280: 2159–2164.
Liu G, Nozell S, Xiao H, Chen X . (2004). Mol Cell Biol 24: 487–501.
Melino G, De Laurenzi V, Vousden KH . (2002). Nat Rev Cancer 2: 605–615.
Molkentin JD, Olson EN . (1996). CurrOpin GenetDev 6: 445–453.
Pediconi N, Lanari A, Costanzo A, Belloni L, Gallo R, Cimino L et al. (2003). Nat Cell Biol 5: 552–558.
Porrello A, Cerone MA, Coen S, Gurtner A, Fontemaggi G, Cimino L et al. (2000). J Cell Biol 151: 1295–1304.
Pozniak CD, Barnabe-Heider F, Rymar VV, Lee AF, Sadikot AF, Miller FD . (2002). J Neurosci 22: 9800–9809.
Pozniak CD, Radinovic S, Yang A, McKeon F, Kaplan DR, Miller FD . (2000). Science 289: 304–306.
Puri PL, Bhakta K, Wood LD, Costanzo A, Zhu J, Wang JY . (2002). Nat Genet 32: 585–593.
Rentzsch F, Kramer C, Hammerschmidt M . (2003). Gene 323: 19–30.
Sartorelli V, Puri PL, Hamamori Y, Ogryzko V, Chung G, Nakatani Y et al. (1999). Mol Cell 4: 725–734.
Tschan MP, Grob TJ, Peters UR, Laurenzi VD, Huegli B, Kreuzer KA et al. (2000). Biochem Biophys Res Commun 277: 62–65.
Vossio S, Palescandolo E, Pediconi N, Moretti F, Balsano C, Levrero M et al. (2002). Oncogene 21: 3796–3803.
Wang J, Walsh K . (1996). Science 273: 359–361.
Wu Z, Woodring PJ, Bhakta KS, Tamura K, Wen F, Feramisco JR et al. (2000). Mol Cell Biol 20: 3951–3964.
Yang A, Walker N, Bronson R, Kaghad M, Oosterwegel M, Bonnin J et al. (2000). Nature 404: 99–103.
Acknowledgements
This work was supported by grants from AIRC and MIUR-FIRB (to ML and GB), European Community (LSHC-CT-2004-503576 to ML and GB), Telethon (To GB and ML) and MIUR-Cofin and Schering-Plough (to ML). LB and PM were supported by a fellowship from the Fondazione A. Cesalpino. FM was supported by a fellowship from FIRC. AD was supported by a fellowship from EMBO.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Belloni, L., Moretti, F., Merlo, P. et al. DNp73α protects myogenic cells from apoptosis. Oncogene 25, 3606–3612 (2006). https://doi.org/10.1038/sj.onc.1209321
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209321
Keywords
This article is cited by
-
Crocetin exploits p53-induced death domain (PIDD) and FAS-associated death domain (FADD) proteins to induce apoptosis in colorectal cancer
Scientific Reports (2016)
-
The sodium/iodide symporter NIS is a transcriptional target of the p53-family members in liver cancer cells
Cell Death & Disease (2013)
-
p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis
Nature Reviews Cancer (2013)
-
p53-paralog DNp73 oncogene is repressed by IFNα/STAT2 through the recruitment of the Ezh2 polycomb group transcriptional repressor
Oncogene (2011)
-
miR-24–mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells
Nature Structural & Molecular Biology (2009)
