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Nucleic Acids Research Advance Access published online on December 7, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl1075
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© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

The p16INK4a tumor suppressor controls p21WAF1 induction in response to ultraviolet light

Mai A. Al-Mohanna, Huda H. Al-Khalaf, Nujoud Al-Yousef and Abdelilah Aboussekhra*

King Faisal Specialist Hospital and Research Center, Department of Biological and Medical Research MBC # 03-66, PO BOX 3354, Riyadh 11211, KSA

*To whom correspondence should be addressed. Tel: +966 1 464 7272, ext. 32840; Fax: +966 1 442 7858; Email: aboussekhra{at}kfshrc.edu.sa

Received October 11, 2006. Accepted November 13, 2006.

p16INK4a and p21WAF1, two major cyclin-dependent kinase inhibitors, are the products of two tumor suppressor genes that play important roles in various cellular metabolic pathways. p21WAF1 is up-regulated in response to different DNA damaging agents. While the activation of p21WAF1 is p53-dependent following {gamma}-rays, the effect of ultraviolet (UV) light on p21WAF1 protein level is still unclear. In the present report, we show that the level of the p21WAF1 protein augments in response to low UVC fluences in different mammalian cells. This up-regulation is mediated through the stabilization of p21WAF1 mRNA in a p16INK4a-dependent manner in both human and mouse cells. Furthermore, using p16-siRNA treated human skin fibroblast; we have shown that p16 controls the UV-dependent cytoplasmic accumulation of the mRNA binding HuR protein. In addition, HuR immunoprecipitations showed that UV-dependent binding of HuR to p21 mRNA is p16-related. This suggests that p16 induces p21 by enabling the relocalization of HuR from the nucleus to the cytoplasm. Accordingly, we have also shown that p16 is necessary for efficient UV-dependent p53 up-regulation, which also requires HuR. These results indicate that, in addition to its role in cell proliferation, p16INK4a is also an important regulator of the cellular response to UV damage.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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