Abstract
p21WAF1/CIP1 is an important transcriptional target of p53 and it plays a critical role in growth arrest after DNA damage. Here, we report the identification of a novel alternate mouse p21 transcript that is conserved in evolution. It differs from the classical p21WAF1/CIP1 transcript in the first exon, which is located at approximately 2.8âkb upstream of transcriptional start site of p21WAF1/CIP1 and is sandwiched between two p53 binding sites. This novel p21 transcript is present in most mouse tissues with highest levels of expression in the spleen. In contrast to the classical p21WAF1/CIP1 transcript, this new transcript is highly dependent on p53 for its basal expression, as evidenced by its absence in nearly all of p53â/â mouse tissues. This transcript is also absent at nonpermissive temperature in a 10-1 mouse cell line lacking endogenous p53 and harboring temperature-sensitive p53 mutant. However, this novel transcript is induced to appreciable levels in the presence of high p53 activity at the permissive temperature. Our data suggest that p53-dependent induction of p21 may be an additive effect conferred by individual increases in the alternate and classical p21 transcripts.
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Acknowledgements
We thank Ying Sun for excellent technical assistance, Aleksandra J Poole and Wenjun Bie for assistance in preparation of RNA from mouse tissues. This work was supported by IDPH Grant (ALG) and NIH Grant CA91146-01A1 (ALG), and NIH Grant DK56283 (ALT).
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Gartel, A., Radhakrishnan, S., Serfas, M. et al. A novel p21WAF1/CIP1 transcript is highly dependent on p53 for its basal expression in mouse tissues. Oncogene 23, 8154â8157 (2004). https://doi.org/10.1038/sj.onc.1207820
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DOI: https://doi.org/10.1038/sj.onc.1207820