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Molecular and Cellular Biology, February 2000, p. 760-769, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

HuR Regulates p21 mRNA Stabilization by UV Light

Wengong Wang,1 Henry Furneaux,2 Huiming Cheng,2 M. Craig Caldwell,1 Dorothy Hutter,1 Yusen Liu,1 Nikki Holbrook,1 and Myriam Gorospe1,*

Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224,1 and Program in Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York 100212

Received 24 September 1999/Accepted 1 November 1999

Expression of the cyclin-dependent kinase inhibitor p21 is highly induced by many stresses, including exposure to short-wavelength UV light (UVC), which increases p21 mRNA stability. Investigation into the mechanisms underlying this stabilization process revealed that proteins present in cytoplasmic lysates of human RKO colorectal carcinoma cells formed complexes with p21 mRNA that were inducible by treatment with UVC and other stress agents. The ubiquitous Elav-type RNA-binding protein HuR was identified within the p21 mRNA-protein complexes, as antibodies recognizing HuR supershifted these complexes and revealed HuR-immunoreactive proteins complexing with p21 mRNA on Western blots. Lowering of endogenous HuR levels through expression of antisense HuR decreased p21 RNA-protein complexes, greatly reduced the UVC inducibility and half-life of p21 mRNA, and prevented UVC-mediated induction of luciferase activity in p21 3' untranslated region-containing reporter constructs. Our findings indicate that HuR plays a major role in regulating stress-induced p21 expression by enhancing p21 mRNA stability and that these effects are coupled to HuR's elevated presence in the cytoplasm.

* Corresponding author. Mailing address: Box 12, LBC, NIA, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825. Phone: (410) 558-8443. Fax: (410) 558-8386. E-mail: myriam-gorospe{at}nih.gov.

Molecular and Cellular Biology, February 2000, p. 760-769, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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