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Molecular and Cellular Biology, July 1999, p. 4825-4831, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

p53 Mediates Apoptotic Crisis in Primary Abelson Virus-Transformed Pre-B Cells

Indira Unnikrishnan,1 Arash Radfar,2,3 Jenia Jenab-Wolcott,2,3 and Naomi Rosenberg1,2,3,4,*

Department of Pathology,1 Immunology Program,2 M.D./Ph.D. Program,3 and Department of Microbiology and Molecular Biology,4 Tufts University School of Medicine, Boston, Massachusetts 02111

Received 22 December 1998/Returned for modification 1 February 1999/Accepted 22 April 1999

Transformation of pre-B cells by Abelson murine leukemia virus (Ab-MLV) involves a balance between positive, growth-stimulatory signals from the v-Abl oncoprotein and negative regulatory cues from cellular genes. This phenomenon is reflected by the clonal selection that occurs during Ab-MLV-mediated transformation in vivo and in vitro. About 50% of all Ab-MLV-transformed pre-B cells express mutant forms of p53 as they emerge from this process, suggesting that this protein may play an important role in the transformation process. Consistent with this idea, expression of p19Arf, a protein whose function depends on the presence of a functional p53, is required for the apoptotic crisis that characterizes primary Ab-MLV transformants. To test the role of p53 in pre-B-cell transformation directly, we examined the response of Trp53-/- mice to Ab-MLV. The absence of p53 shortens the latency of Abelson disease induction but does not affect the frequency of cells susceptible to Ab-MLV-induced transformation. However, primary transformants derived from the null animals bypass the apoptotic crisis that characterizes the transition from primary transformant to fully malignant cell line. These effects do not require p21Cip-1, a major downstream target of p53; however, consistent with a role of p19Arf, transformants expressing mutant p53 and abundant p19 retain wild-type p19 sequences.

* Corresponding author. Mailing address: SC315, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-6906. Fax: (617) 636-0337. E-mail: nrosenbe{at}opal.tufts.edu.

Molecular and Cellular Biology, July 1999, p. 4825-4831, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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