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

Abelson murine leukemia virus (A-MuLV) is an acute transforming retrovirus that preferentially transforms early B-lineage cells both in vivo and in vi tro. 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 o f v-Abl without affecting the fibroblast-transforming ability. In this stud y we have determined the abilities of both wild-type and C-terminally trunc ated (p90) forms of v-Abl to transform cells from p53(-/-) mice, Lack of p5 3 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 B2 20(+) IgM(-) pre-B cells. p53-deficient mice have earlier tumor onset, more rapid tumor progression, and decreased survival time following A-MuLV infe ction, but all of the tumors are pre-B lymphomas, Thus, p53-dependent pathw ays inhibit v-Abl transformation but play no role in conferring preferentia l transformation of pre-B cells. Surprisingly, the C-terminally truncated f orm of v-Abl (p90) transforms pre-B cells very efficiently in mice larking p53, thus demonstrating that the C terminus of v-Abl does not determine pre B tropism but is necessary to overcome p53-dependent inhibition of transfor mation.