title: 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.
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.
authors.affiliation: Departments of Biochemistry, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zou
authors.forename: F
authors.initials: F
authors.lastname: Cong
authors.forename: M
authors.initials: M
authors.lastname: Coutts
authors.forename: G
authors.initials: G
authors.lastname: Cattoretti
authors.forename: S P
authors.initials: SP
authors.lastname: Goff
authors.forename: K
authors.initials: K
authors.lastname: Calame
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009052:Leukemia Virus, Murine / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D008223:Lymphoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016374:Oncogene Proteins v-abl / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D016374:Oncogene Proteins v-abl; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53