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Cancers 2018, 10(3), 78; https://doi.org/10.3390/cancers10030078

New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response

1
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany
2
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA
3
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA
These authors contributed equal to this work.
*
Author to whom correspondence should be addressed.
Received: 24 February 2018 / Revised: 15 March 2018 / Accepted: 16 March 2018 / Published: 18 March 2018
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Abstract

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. View Full-Text
Keywords: Protein Kinase B; Akt; PI3K; cellular radiation response; signaling network; Akt targets Protein Kinase B; Akt; PI3K; cellular radiation response; signaling network; Akt targets
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Szymonowicz, K.; Oeck, S.; Malewicz, N.M.; Jendrossek, V. New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response. Cancers 2018, 10, 78.

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