A ROLE FOR C-ABL IN C-MYC REGULATION

c-Abl, a nonreceptor tyrosine kinase, appears to play a role in cell c ycle progression, cell proliferation and differentiation. Mice homozyg ous for a mutation in c-abl (abl(ml)), show pleiotropic abnormalities, including neonatal death, developmental defects, susceptibility to in fection and dehydration (Schwartzberg et al., 1991). However, the exac t substrates of c-Abl and the signal transduction pathways it might in itiate are not known. We have examined how c-Abl affects c-myc express ion by studying abl(ml) mice. Quantitative riboprobe analyses demonstr ated that in the heart, liver, thymus, brain, testes, intestines and l ung, there were no differences in the-steady-state level of c-myc RNA between the abl(ml) mice and Littermate controls. However, in adrenal glands, kidneys and splenic B cells, c-myc RNA levels were decreased a pproximately 50% compared to littermate controls. Induction of c-myc m RNA following activation of splenic B cells with LPS is also defective in abl(ml) splenocytes. Finally, me show that c-Abl can directly tran sactivate c-myc transcription. These results suggest that c-Abl is inv olved in the normal transcription regulation of c-myc in selected tiss ues and that decreased c-myc RNA could be one cause of abnormalities i n the abl(ml) mice.