Abstract
The p53 tumor-suppressor is a transcription factor that is stabilized in response to cellular stress leading to growth arrest or apoptosis. p21WAF1/CIP1 is a major transcriptional target of p53 and it plays a critical role in p53-dependent cell cycle arrest. In this study, we identified multiple alternate human p21 transcripts that have their transcriptional start sites in the direct proximity of the distal p53 response element. These transcripts are upregulated as a result of DNA damage-induced p53 activation. Furthermore, the basal expression of these alternate transcripts is strongly regulated by p53 and they are undetectable in p53-knocked down cells. This is in contrast to classical p21 transcripts, which have reduced, albeit detectable expression levels in the absence of p53. The existence of the alternate transcripts underscores the complexity of the human p21 genomic locus and opens up new avenues for further investigation.
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
Accession codes
References
Bartel F, Taubert H, Harris LC . (2002). Cancer Cell 2: 9–15.
Chen B, He L, Savell VH, Jenkins JJ, Parham DM . (2000). Cancer Res 60: 3290–3298.
Chipuk JE, Maurer U, Green DR, Schuler M . (2003). Cancer Cell 4: 371–381.
Claus R, Lubbert M . (2003). Oncogene 22: 6489–6496.
el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM et al. (1993). Cell 75: 817–825.
El-Deiry WS . (2003). Oncogene 22: 7486–7495.
Gartel AL, Radhakrishnan SK . (2005). Cancer Res 65: 3980–3985.
Gartel AL, Tyner AL . (1999). Exp Cell Res 246: 280–289.
Gartel AL, Radhakrishnan SK, Serfas MS, Kwon YH, Tyner AL . (2004). Oncogene 23: 8154–8157.
Gartel AL, Serfas MS, Tyner AL . (1996). Proc Soc Exp Biol Med 213: 138–149.
Giaccia AJ, Kastan MB . (1998). Genes Dev 12: 2973–2983.
Jeffers JR, Parganas E, Lee Y, Yang C, Wang J, Brennan J et al. (2003). Cancer Cell 4: 321–328.
Kaeser MD, Pebernard S, Iggo RD . (2004). J Biol Chem 279: 7598–7605.
Kubbutat MH, Jones SN, Vousden KH . (1997). Nature 387: 299–303.
Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE et al. (1994). Science 266: 807–810.
Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P et al. (2003). Mol Cell 11: 577–590.
Nakano K, Vousden KH . (2001). Mol Cell 7: 683–694.
Nozell S, Chen X . (2002). Oncogene 21: 1285–1294.
Phelps DE, Hsiao KM, Li Y, Hu N, Franklin DS, Westphal E et al. (1998). Mol Cell Biol 18: 2334–2343.
Slee EA, O'Connor DJ, Lu X . (2004). Oncogene 23: 2809–2818.
Tang HY, Zhao K, Pizzolato JF, Fonarev M, Langer JC, Manfredi JJ . (1998). J Biol Chem 273: 29156–29163.
Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B . (2001). Mol Cell 7: 673–682.
Zhu WG, Srinivasan K, Dai Z, Duan W, Druhan LJ, Ding H et al. (2003). Mol Cell Biol 23: 4056–4065.
Acknowledgements
This work was supported by NIH Grant CA91146 to ALG. We thank Dr Gudkov for the short hairpin RNA expressing construct targeting p53 and Dr Yu for the anti-PUMA antibodies.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Radhakrishnan, S., Gierut, J. & Gartel, A. Multiple alternate p21 transcripts are regulated by p53 in human cells. Oncogene 25, 1812–1815 (2006). https://doi.org/10.1038/sj.onc.1209195
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209195
Keywords
This article is cited by
-
Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors
Clinical Epigenetics (2012)
-
The relationship between transcription initiation RNAs and CCCTC-binding factor (CTCF) localization
Epigenetics & Chromatin (2011)
-
EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis
Molecular Cancer (2010)
-
p53 regulates maternal reproduction through LIF
Nature (2007)