New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response
Genetic alterations driving aberrant activation of the survival kinase Protein Kinase B (Akt) are observed with high frequency during malignant transformation and cancer progression. Oncogenic gene mutations coding for the upstream regulators or Akt, e.g., growth factor receptors, RAS and phosphatid...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-03-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/10/3/78 |
| _version_ | 1797707943283523584 |
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| author | Klaudia Szymonowicz Sebastian Oeck Nathalie M. Malewicz Verena Jendrossek |
| author_facet | Klaudia Szymonowicz Sebastian Oeck Nathalie M. Malewicz Verena Jendrossek |
| author_sort | Klaudia Szymonowicz |
| collection | DOAJ |
| description | Genetic alterations driving aberrant activation of the survival kinase Protein Kinase B (Akt) are observed with high frequency during malignant transformation and cancer progression. Oncogenic gene mutations coding for the upstream regulators or Akt, e.g., growth factor receptors, RAS and phosphatidylinositol-3-kinase (PI3K), or for one of the three Akt isoforms as well as loss of the tumor suppressor Phosphatase and Tensin Homolog on Chromosome Ten (PTEN) lead to constitutive activation of Akt. By activating Akt, these genetic alterations not only promote growth, proliferation and malignant behavior of cancer cells by phosphorylation of various downstream signaling molecules and signaling nodes but can also contribute to chemo- and radioresistance in many types of tumors. Here we review current knowledge on the mechanisms dictating Akt’s activation and target selection including the involvement of miRNAs and with focus on compartmentalization of the signaling network. Moreover, we discuss recent advances in the cross-talk with DNA damage response highlighting nuclear Akt target proteins with potential involvement in the regulation of DNA double strand break repair. |
| first_indexed | 2024-03-12T06:15:02Z |
| format | Article |
| id | doaj.art-b1578d94b899457883955c23e416d6af |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:15:02Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b1578d94b899457883955c23e416d6af2023-09-03T02:44:39ZengMDPI AGCancers2072-66942018-03-011037810.3390/cancers10030078cancers10030078New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation ResponseKlaudia Szymonowicz0Sebastian Oeck1Nathalie M. Malewicz2Verena Jendrossek3Institute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, 45122 Essen, GermanyInstitute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, 45122 Essen, GermanyDepartment of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USAInstitute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, 45122 Essen, GermanyGenetic alterations driving aberrant activation of the survival kinase Protein Kinase B (Akt) are observed with high frequency during malignant transformation and cancer progression. Oncogenic gene mutations coding for the upstream regulators or Akt, e.g., growth factor receptors, RAS and phosphatidylinositol-3-kinase (PI3K), or for one of the three Akt isoforms as well as loss of the tumor suppressor Phosphatase and Tensin Homolog on Chromosome Ten (PTEN) lead to constitutive activation of Akt. By activating Akt, these genetic alterations not only promote growth, proliferation and malignant behavior of cancer cells by phosphorylation of various downstream signaling molecules and signaling nodes but can also contribute to chemo- and radioresistance in many types of tumors. Here we review current knowledge on the mechanisms dictating Akt’s activation and target selection including the involvement of miRNAs and with focus on compartmentalization of the signaling network. Moreover, we discuss recent advances in the cross-talk with DNA damage response highlighting nuclear Akt target proteins with potential involvement in the regulation of DNA double strand break repair.http://www.mdpi.com/2072-6694/10/3/78Protein Kinase BAktPI3Kcellular radiation responsesignaling networkAkt targets |
| spellingShingle | Klaudia Szymonowicz Sebastian Oeck Nathalie M. Malewicz Verena Jendrossek New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response Cancers Protein Kinase B Akt PI3K cellular radiation response signaling network Akt targets |
| title | New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response |
| title_full | New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response |
| title_fullStr | New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response |
| title_full_unstemmed | New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response |
| title_short | New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response |
| title_sort | new insights into protein kinase b akt signaling role of localized akt activation and compartment specific target proteins for the cellular radiation response |
| topic | Protein Kinase B Akt PI3K cellular radiation response signaling network Akt targets |
| url | http://www.mdpi.com/2072-6694/10/3/78 |
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