A role for c-Abl in c-myc regulation
Wong, K.K.; Hardin, J.D.; Boast, S.; Cooper, C.L.; Merrell, K.T.; Doyle, T.G.; Goff, S.P.; Calame, K.L.
Oncogene 10(4): 705-711
1995
ISSN/ISBN: 0950-9232 PMID: 7862448 Document Number: 440107
c-Abl, a nonreceptor tyrosine kinase, appears to play a role in cell cycle progression, cell proliferation and differentiation. Mice homozygous for a mutation in c-abl (abl-m1), show pleiotropic abnormalities, including neonatal death, developmental defects, susceptibility to infection and dehydration (Schwartzberg et al., 1991). However, the exact substrates of c-Abl and the signal transduction pathways it might initiate are not known. We have examined how c-Abl affects c-myc expression by studying abl-m1 mice. Quantitative riboprobe analyses demonstrated that in the heart, liver, thymus, brain, testes, intestines and lung, there were no differences in the steady-state level of c-myc RNA between the abl-m1 mice and littermate controls. However, in adrenal glands, kidneys and splenic B cells, c-myc RNA levels were decreased approximately 50% compared to littermate controls. Induction of c-myc mRNA following activation of splenic B cells with LPS is also defective in abl-m1 splenocytes. Finally, we show that c-Abl can directly transactivate c-myc transcription. These results suggest that c-Abl is involved in the normal transcription regulation of c-myc in selected tissues and that decreased c-myc RNA could be one cause of abnormalities in the abl-m1 mice.