This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Warren, D.
Right arrow Articles by Rosenberg, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Warren, D.
Right arrow Articles by Rosenberg, N.

 Previous Article  |  Next Article 

Journal of Virology, April 2003, p. 4617-4625, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4617-4625.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Extreme Carboxyl Terminus of v-Abl Is Required for Lymphoid Cell Transformation by Abelson Virus

David Warren,1,{dagger} Deborah S. Griffin,2 Celine Mainville,2,3,{ddagger} and Naomi Rosenberg1,2,3*

Department of Molecular Biology and Microbiology,1 Department of Pathology,2 the Graduate Program in Immunology, Tufts University School of Medicine, Boston, Massachusetts 021113

Received 14 October 2002/ Accepted 16 January 2003

The v-Abl protein tyrosine kinase encoded by Abelson murine leukemia virus (Ab-MLV) induces transformation of pre-B cells in vivo and in vitro and can transform immortalized fibroblast cell lines in vitro. Although the kinase activity of the protein is required for these events, most previously studied mutants encoding truncated v-Abl proteins that lack the extreme carboxyl terminus retain high transforming capacity in NIH 3T3 cells but transform lymphocytes poorly. To understand the mechanisms responsible for poor lymphoid transformation, mutants expressing a v-Abl protein lacking portions of the COOH terminus were compared for their ability to transform pre-B cells. Although all mutants lacking sequences within the COOH terminus were compromised for lymphoid transformation, loss of amino acids in the central region of the COOH terminus, including those implicated in JAK interaction and DNA binding, decreased transformation twofold or less. In contrast, loss of the extreme COOH terminus rendered the protein unstable and led to rapid proteosome-mediated degradation, a feature that was more prominent when the protein was expressed in Ab-MLV-transformed lymphoid cells. These data indicate that the central portion of the COOH terminus is not essential for lymphoid transformation and reveal that one important function of the COOH terminus is to stabilize the v-Abl protein in lymphoid cells.

* 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.

{dagger} Present address: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912.

{ddagger} Present address: Affymetrix, Bedford, MA 01730.

Journal of Virology, April 2003, p. 4617-4625, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4617-4625.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zimmerman, R. S., Rosenberg, N. (2008). Changes in p19Arf Localization Accompany Apoptotic Crisis during Pre-B-Cell Transformation by Abelson Murine Leukemia Virus. J. Virol. 82: 8383-8391 [Abstract] [Full Text]  
  • Yi, C.-r., Rosenberg, N. (2008). Mutations Affecting the MA Portion of the v-Abl Protein Reveal a Conserved Role of Gag in Abelson Murine Leukemia Virus (MLV) and Moloney MLV. J. Virol. 82: 5307-5315 [Abstract] [Full Text]  
  • 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]  
  • Unnikrishnan, I., Rosenberg, N. (2003). Absence of p53 Complements Defects in Abelson Murine Leukemia Virus Signaling. J. Virol. 77: 6208-6215 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»