Inhibition of Cyclin-Dependent Kinase Phosphorylation of FOXO1 and Prostate Cancer Cell Growth by a Peptide Derived from FOXO1
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 in...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2011-09-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558611800370 |
| _version_ | 1818273192374960128 |
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| author | Huarui Lu Ping Liu Yunqian Pan Haojie Huang |
| author_facet | Huarui Lu Ping Liu Yunqian Pan Haojie Huang |
| author_sort | Huarui Lu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T21:54:03Z |
| format | Article |
| id | doaj.art-ed908a34546c4e7dbc2a7bf4760efb5b |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-12T21:54:03Z |
| publishDate | 2011-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-ed908a34546c4e7dbc2a7bf4760efb5b2022-12-22T00:10:42ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022011-09-0113985486310.1593/neo.11594Inhibition of Cyclin-Dependent Kinase Phosphorylation of FOXO1 and Prostate Cancer Cell Growth by a Peptide Derived from FOXO1Huarui Lu0Ping Liu1Yunqian Pan2Haojie Huang3Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USAIncreasing 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.http://www.sciencedirect.com/science/article/pii/S1476558611800370 |
| spellingShingle | Huarui Lu Ping Liu Yunqian Pan Haojie Huang Inhibition of Cyclin-Dependent Kinase Phosphorylation of FOXO1 and Prostate Cancer Cell Growth by a Peptide Derived from FOXO1 Neoplasia: An International Journal for Oncology Research |
| title | Inhibition of Cyclin-Dependent Kinase Phosphorylation of FOXO1 and Prostate Cancer Cell Growth by a Peptide Derived from FOXO1 |
| title_full | Inhibition of Cyclin-Dependent Kinase Phosphorylation of FOXO1 and Prostate Cancer Cell Growth by a Peptide Derived from FOXO1 |
| title_fullStr | Inhibition of Cyclin-Dependent Kinase Phosphorylation of FOXO1 and Prostate Cancer Cell Growth by a Peptide Derived from FOXO1 |
| title_full_unstemmed | Inhibition of Cyclin-Dependent Kinase Phosphorylation of FOXO1 and Prostate Cancer Cell Growth by a Peptide Derived from FOXO1 |
| title_short | Inhibition of Cyclin-Dependent Kinase Phosphorylation of FOXO1 and Prostate Cancer Cell Growth by a Peptide Derived from FOXO1 |
| title_sort | inhibition of cyclin dependent kinase phosphorylation of foxo1 and prostate cancer cell growth by a peptide derived from foxo1 |
| url | http://www.sciencedirect.com/science/article/pii/S1476558611800370 |
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