Abstract
The tumor suppressor p53 and its target the CDK inhibitor p21 (Cip1/Waf1) are key components of the cellular response to DNA damage. Insight into how p21 is regulated in normal cells, and how it may be deregulated in tumor cells is important for the understanding of tumorigenesis. p21 was induced in normal human diploid fibroblasts after UV irradiation-induced DNA damage, but, at a high dose of UV irradiation, a faster mobility form of p21 on SDS–PAGE (designated p21Δ) was expressed. Surprisingly, in a variety of growing transformed cell lines, the level of p21 was low but p21Δ was prominent. We found that p21Δ appeared to be derived through a loss of around 10 amino acids from the C-terminus of p21, which theoretically would remove the PCNA binding domain, a second cyclin binding domain and the nuclear localization signal sequence. Several characteristics distinguish p21 from p21Δ. Both the full length p21 and p21Δ could be stabilized by a proteasome inhibitor, but only the full length p21 was associated with Cdk2 and PCNA. Consistent with this, gel filtration chromatography revealed that all the full length p21 in the cell was complexed to other proteins, whereas a significant portion of p21Δ was in monomeric form. Moreover, p21 was mainly localized to the nucleus, but p21Δ was mainly localized to the cytoplasm. We propose that the decrease in p21 and increase in p21Δ could contribute to the deregulation of the cell cycle, and could be a mechanism involved in cellular transformation.
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
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Poon, R., Hunter, T. Expression of a novel form of p21Cip1/Waf1 in UV-irradiated and transformed cells. Oncogene 16, 1333–1343 (1998). https://doi.org/10.1038/sj.onc.1201897
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201897
Keywords
This article is cited by
-
Recruitment of trimeric proliferating cell nuclear antigen by G1-phase cyclin-dependent kinases following DNA damage with platinum-based antitumour agents
British Journal of Cancer (2013)
-
Cytoplasmic p21 WAF1/CIP1 expression is correlated with HER-2/ neu in breast cancer and is an independent predictor of prognosis
Breast Cancer Research (2003)
-
Inhibition of Rel/Nuclear Factor-κB signaling in skin results in defective DNA damage-induced cell cycle arrest and Ha-ras- and p53-independent tumor development
Oncogene (2002)
-
F9 embryonal carcinoma cells fail to stop at G1/S boundary of the cell cycle after γ-irradiation due to p21WAF1/CIP1 degradation
Oncogene (2000)
-
Endothelial receptor tyrosine kinases activate the STAT signaling pathway: mutant Tie-2 causing venous malformations signals a distinct STAT activation response
Oncogene (1999)