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Journal of Virology, September 2008, p. 8383-8391, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00348-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Changes in p19Arf Localization Accompany Apoptotic Crisis during Pre-B-Cell Transformation by Abelson Murine Leukemia Virus{triangledown}

Rebekah Stackpole Zimmerman1,2,{dagger} and Naomi Rosenberg1,2,3*

Genetics Graduate Program, Sackler School of Graduate Biomedical Sciences,1 Departments of Pathology,2 Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 021113

Received 18 February 2008/ Accepted 13 June 2008

Transformation by Abelson murine leukemia virus (Ab-MLV) is a multistep process in which growth-stimulatory signals from the v-Abl oncoprotein and growth-suppressive signals from the p19Arf-p53 tumor suppressor pathway oppose each other and influence the outcome of infection. The process involves a proliferative phase during which highly viable primary transformants expand, followed by a period of marked apoptosis (called "crisis") that is dependent on the presence of p19Arf and p53; rare cells that survive this phase emerge as fully transformed and malignant. To understand the way in which v-Abl expression affects p19Arf expression, we examined changes in expression of Arf during all stages of Ab-MLV transformation process. As is consistent with the ability of v-Abl to stimulate Myc, a transcription factor known to induce p19Arf, Myc and Arf are induced soon after infection and p19Arf is expressed. At these early time points, the infected cells remain highly viable. The onset of crisis is marked by an increase in p19Arf expression and a change in localization of the protein from the nucleoplasm to the nucleolus. These data together suggest that the localization and expression levels of p19Arf modulate the effects of the protein during oncogenesis and reveal that the p19Arf-mediated response is subject to multiple layers of regulation that influence its function during Ab-MLV-mediated transformation.

* Corresponding author. Mailing address: Sackler 814, Tufts Medical School, 136 Harrison Avenue, Boston, MA 02111. Phone: (617) 636-2143. Fax: (617) 636-0337. E-mail: naomi.rosenberg{at}tufts.edu

{triangledown} Published ahead of print on 25 June 2008.

{dagger} Present address: Harvard-Partners Center for Genetics and Genomics, Cambridge, MA 02139.

Journal of Virology, September 2008, p. 8383-8391, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00348-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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