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A Transformation-Defective Polyomavirus Middle T Antigen with a Novel Defect in PI3 Kinase Signaling

Overview
Journal J Virol
Date 2016 Nov 18
PMID 27852846
Citations 2
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Abstract

Importance: The gene coding for middle T antigen (MT) is the murine polyomavirus oncogene most responsible for tumor formation. Its study has a history of uncovering novel aspects of mammalian cell regulation. The importance of PI3K activity and tyrosine phosphorylation are two examples of insights coming from MT. This study describes new mutants unable to transform like the wild type that point to novel regulation of PI3K signaling. Previous mutants were defective in PI3K because they failed to bind the enzyme and bring the activity to the membrane. These mutants recruit PI3K activity like the wild type, but fail to elevate the cellular level of PIP3, the product used to signal downstream of PI3K. As a result, they fail to activate either Akt or Rac1, explaining the transformation defect.

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References
1.
Walter G, RUEDIGER R, Slaughter C, Mumby M . Association of protein phosphatase 2A with polyoma virus medium tumor antigen. Proc Natl Acad Sci U S A. 1990; 87(7):2521-5. PMC: 53721. DOI: 10.1073/pnas.87.7.2521. View

2.
Maroulakou I, Oemler W, Naber S, Tsichlis P . Akt1 ablation inhibits, whereas Akt2 ablation accelerates, the development of mammary adenocarcinomas in mouse mammary tumor virus (MMTV)-ErbB2/neu and MMTV-polyoma middle T transgenic mice. Cancer Res. 2007; 67(1):167-77. DOI: 10.1158/0008-5472.CAN-06-3782. View

3.
Carmichael G, Schaffhausen B, Dorsky D, Oliver D, BENJAMIN T . Carboxy terminus of polyoma middle-sized tumor antigen is required for attachment to membranes, associated protein kinase activities, and cell transformation. Proc Natl Acad Sci U S A. 1982; 79(11):3579-83. PMC: 346465. DOI: 10.1073/pnas.79.11.3579. View

4.
Rouleau C, Pores Fernando A, Hwang J, Faure N, Jiang T, White E . Transformation by Polyomavirus Middle T Antigen Involves a Unique Bimodal Interaction with the Hippo Effector YAP. J Virol. 2016; 90(16):7032-7045. PMC: 4984622. DOI: 10.1128/JVI.00417-16. View

5.
Hwang J, Jiang T, Kulkarni S, Faure N, Schaffhausen B . Protein phosphatase 2A isoforms utilizing Aβ scaffolds regulate differentiation through control of Akt protein. J Biol Chem. 2013; 288(44):32064-73. PMC: 3814800. DOI: 10.1074/jbc.M113.497644. View