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Molecular and Cellular Biology, January 2000, p. 628-633, Vol. 20, No. 2
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

p53 Deficiency Increases Transformation by v-Abl and Rescues the Ability of a C-Terminally Truncated v-Abl Mutant To Induce Pre-B Lymphoma In Vivo

Xiaoming Zou,1 Feng Cong,1 Margaret Coutts,2 Giorgio Cattoretti,3 Stephen P. Goff,1,2,4 and Kathryn Calame1,2,*

Departments of Biochemistry and Molecular Biophysics,1 Microbiology,2 and Pathology3 and Howard Hughes Medical Institute,4 Columbia University College of Physicians and Surgeons, New York, New York 10032

Received 6 April 1999/Returned for modification 28 April 1999/Accepted 15 October 1999

Abelson murine leukemia virus (A-MuLV) is an acute transforming retrovirus that preferentially transforms early B-lineage cells both in vivo and in vitro. Its transforming protein, v-Abl, is a tyrosine kinase related to v-Src but containing an extended C-terminal domain. Many mutations affecting the C-terminal portion of the molecule block the pre-B-transforming activity of v-Abl without affecting the fibroblast-transforming ability. In this study we have determined the abilities of both wild-type and C-terminally truncated (p90) forms of v-Abl to transform cells from p53-/- mice. Lack of p53 increases the susceptibility of bone marrow cells to transformation by v-Abl by a factor of more than 7 but does not alter v-Abl's preference for B220+ IgM- pre-B cells. p53-deficient mice have earlier tumor onset, more rapid tumor progression, and decreased survival time following A-MuLV infection, but all of the tumors are pre-B lymphomas. Thus, p53-dependent pathways inhibit v-Abl transformation but play no role in conferring preferential transformation of pre-B cells. Surprisingly, the C-terminally truncated form of v-Abl (p90) transforms pre-B cells very efficiently in mice lacking p53, thus demonstrating that the C terminus of v-Abl does not determine preB tropism but is necessary to overcome p53-dependent inhibition of transformation.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University, 701 West 168th St., HHSC 1202, New York, NY 10032. Phone: (212) 305-3504. Fax: (212) 305-1468. E-mail: klc1{at}columbia.edu.

Molecular and Cellular Biology, January 2000, p. 628-633, Vol. 20, No. 2
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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