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Journal of Virology, February 2004, p. 1636-1644, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1636-1644.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Active Akt and Functional p53 Modulate Apoptosis in Abelson Virus-Transformed Pre-B Cells

Li Gong,^1,2 Indira Unnikrishnan,^3, Anuradha Raghavan,^3,4 Kalindi Parmar,^3, and Naomi Rosenberg^1,2,3,4*

Department of Molecular Biology and Microbiology,¹ Department of Pathology,³ School of Medicine and Molecular Microbiology and Immunology Graduate Programs,² Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts 02111⁴

Received 12 August 2003/ Accepted 8 October 2003

Suppression of apoptosis is an important feature of the Abelson murine leukemia virus (Ab-MLV) transformation process. During multistep transformation, Ab-MLV-infected pre-B cells undergo p53-dependent apoptosis during the crisis phase of transformation. Even once cells are fully transformed, an active v-Abl protein tyrosine kinase is required to suppress apoptosis because cells transformed by temperature-sensitive (ts) kinase mutants undergo rapid apoptosis after a shift to the nonpermissive temperature. However, inactivation of the v-Abl protein by a temperature shift interrupts signals transmitted via multiple pathways, making it difficult to identify those that are critically important for the suppression of apoptosis. To begin to dissect these pathways, we tested the ability of an SH2 domain Ab-MLV mutant, P120/R273K, to rescue aspects of the ts phenotype of pre-B cells transformed by the conditional kinase domain mutant. The P120/R273K mutant suppressed apoptosis at the nonpermissive temperature, a phenotype correlated with its ability to activate Akt. Apoptosis also was suppressed at the nonpermissive temperature by constitutively active Akt and in p53-null pre-B cells transformed with the ts kinase domain mutant. These data indicate that an intact Src homology 2 (SH2) domain is not critical for apoptosis suppression and suggest that signals transmitted through Akt and p53 play an important role in the response.

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* Corresponding author. Mailing address: Jaharis 808, Tufts Medical School, 150 Harrison Ave., Boston, MA 02111. Phone: (617) 636-2143. Fax: (617) 636-0337. E-mail: naomi.rosenberg{at}tufts.edu.

Present address: Iconix Pharmaceuticals, Mountain View, CA 94043.

Present address: Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107.

Present address: Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA 02215.

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Journal of Virology, February 2004, p. 1636-1644, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1636-1644.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Yi, C.-R., Rosenberg, N. (2007). Gag Influences Transformation by Abelson Murine Leukemia Virus and Suppresses Nuclear Localization of the v-Abl Protein. J. Virol. 81: 9461-9468 [Abstract] [Full Text]  
• Baughn, L. B., Rosenberg, N. (2005). Disruption of the Shc/Grb2 Complex during Abelson Virus Transformation Affects Proliferation, but Not Apoptosis. J. Virol. 79: 2325-2334 [Abstract] [Full Text]