Inhibition of cyclin-dependent kinase phosphorylation of FOXO1 and prostate cancer cell growth by a peptide derived from FOXO1

Huarui Lu, Ping Liu, Yunqian Pan, Haojie Huang

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26 Scopus citations


Increasing evidence suggests that FOXO1 possesses a tumor suppressor function. Inactivation of FOXO1 has been documented in many types of human cancer, and restoring the activity of FOXO1 holds promise for cancer treatment. In this study, we identified a FOXO1-derived peptide termed FO1-6nls that inhibits cyclin-dependent kinases 1 and 2 (CDK1/2)-mediated phosphorylation of FOXO1 at the serine 249 residue in vitro and in vivo. Overexpression of FO1-6nls in prostate cancer (PCa) cells not only blocked CDK1-induced cytoplasmic localization of FOXO1 but also augmented FOXO1's transcriptional activity. This effect of FO1-6nls requires its binding to CDK1 and CDK2. Moreover, the ectopic expression of FO1-6nls inhibited the growth of PTEN-positive DU145 PCa cells. Importantly, the growth-inhibitory function of FO1-6nls is dependent on FOXO1. Finally, the ectopic expression of FO1-6nls overcame CDK1-mediated inhibition of FOXO1-induced apoptosis of PCa cells. These results indicate that the FOXO1-derived peptide FO1-6nls can restore FOXO1's tumor suppressor function by specifically opposing CDK1/2-mediated phosphorylation and inhibition of FOXO1 and hence may have a therapeutic potential for the treatment of PCa.

Original languageEnglish (US)
Pages (from-to)854-863
Number of pages10
Issue number9
StatePublished - Sep 2011

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Abbreviations: CDK, cyclin-dependent kinase; PCa, prostate cancer; nls, nuclear localization signal; GST, glutathione S-transferase Address all correspondence to: Haojie Huang, PhD, Department of Pathology, Stony Brook University Medical Center, BST 9-151, Stony Brook, NY 11794. E-mail: 1This work was supported in part by funds from the National Institutes of Health (CA134514 and CA130908 to H.H.). Received 28 April 2011; Revised 26 June 2011; Accepted 27 June 2011 Copyright © 2011 Neoplasia Press, Inc. All rights reserved 1522-8002/11/$25.00 DOI 10.1593/neo.11594


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