c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets.
We report here that the expression of virtually all proposed c-Myc target genes is unchanged in cells containing a homozygous null deletion of c-myc. Two noteworthy exceptions are the gene cad, which has reduced log phase expression and serum induction in c-myc null cells, and the growth arrest gene gadd45, which is derepressed by c-myc knockout. Thus, cad and gadd45 are the only proposed targets of c-Myc that may contribute to the dramatic slow growth phenotype of c-myc null cells. Our results demonstrate that a loss-of-function approach is critical for the evaluation of potential c-Myc target genes.
Bush
A
A
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544 USA.
Mateyak
M
M
Dugan
K
K
Obaya
A
A
Adachi
S
S
Sedivy
J
J
Cole
M
M
D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D004080:Dihydroorotase / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D039561:Eukaryotic Initiation Factor-4E; D017353:Gene Deletion; D005786:Gene Expression Regulation; D016259:Genes, myc; D016158:Genes, p53; D006720:Homozygote; D047908:Intracellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000235:genetics; D010448:Peptide Initiation Factors / Q000235:genetics; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D051381:Rats; D020687:cdc25 Phosphatases; D000097642:GADD45 Proteins
D001221:Aspartate Carbamoyltransferase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D004080:Dihydroorotase; D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D009955:Ornithine Decarboxylase; D010448:Peptide Initiation Factors; D017027:Protein Tyrosine Phosphatases; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D020687:cdc25 Phosphatases; D000097642:GADD45 Proteins; C033626:CAD trifunctional enzyme; C517007:Cdc25a protein, rat