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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

p53 Deficiency Increases Transformation by v-Abl and Rescues the Ability of a C-Terminally... 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 Calame 1 , 2 , * Departments of Biochemistry and Molecular Biophysics, 1 Microbiology, 2 and Pathology 3 and Howard Hughes Medical Institute, 4 Columbia University College of Physicians and Surgeons, New York, New York 10032 ABSTRACT 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

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

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

Molecular and Cellular Biology , Volume 20 (2): 628 – Jan 15, 2000

Abstract

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 Calame 1 , 2 , * Departments of Biochemistry and Molecular Biophysics, 1 Microbiology, 2 and Pathology 3 and Howard Hughes Medical Institute, 4 Columbia University College of Physicians and Surgeons, New York, New York 10032 ABSTRACT 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.

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Publisher
American Society For Microbiology
Copyright
Copyright © 2000 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
DOI
10.1128/MCB.20.2.628-633.2000
Publisher site
See Article on Publisher Site

Abstract

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 Calame 1 , 2 , * Departments of Biochemistry and Molecular Biophysics, 1 Microbiology, 2 and Pathology 3 and Howard Hughes Medical Institute, 4 Columbia University College of Physicians and Surgeons, New York, New York 10032 ABSTRACT 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.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Jan 15, 2000

References