A role for c-Abl in c-myc regulation.
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 (ablml), 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 ablml 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 ablml 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 ablml 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 ablml mice.
Wong
K K
KK
Integrated Program in Cellular, Columbia University College of Physicians and Surgeons, New York, New York.
Hardin
J D
JD
Boast
S
S
Cooper
C L
CL
Merrell
K T
KT
Doyle
T G
TG
Goff
S P
SP
Calame
K L
KL
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle; D005786:Gene Expression Regulation; D016313:Genes, abl; D016259:Genes, myc; D007668:Kidney / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D012333:RNA, Messenger; D016315:Proto-Oncogene Proteins c-abl