The c-Myc Oncoprotein Interacts with Bcr.
Bcr is a multifunctional protein that is the fusion partner for Abl (p210 Bcr-Abl) in Philadelphia chromosome positive leukemias. We have identified c-Myc as a binding partner for Bcr in both yeast and mammalian cells. We are also able to observe interactions between natively expressed c-Myc and Bcr in leukemic cell lines. Although Bcr and Max have overlapping binding sites on c-Myc, Bcr cannot interact with Max, or with the c-Myc.Max heterodimer. Bcr expression blocks activation of c-Myc-responsive genes, as well as the transformed phenotype induced by coexpression of c-Myc and H-Ras, and this finding suggests that one function of Bcr is to limit the activity of c-Myc. However, Bcr does not block c-Myc function by preventing its nuclear localization. Interestingly, increased Bcr dosage in COS-7 and K-562 cells correlates with a reduction in c-Myc protein levels, suggesting that Bcr may in fact be limiting c-Myc activity by regulating its stability. These data indicate that Bcr is a novel regulator of c-Myc function whose disrupted expression may contribute to the high level of c-Myc protein that is observed in Bcr-Abl transformed cells.
Mahon
Gwendolyn M
GM
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, PO Box 1709, 225 Warren Street, Newark, NJ 07101-1709, USA.
Wang
Yan
Y
Korus
Malgorzata
M
Kostenko
Elena
E
Cheng
Li
L
Sun
Tong
T
Arlinghaus
Ralph B
RB
Whitehead
Ian P
IP
D000818:Animals; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015003:Yeasts / Q000378:metabolism
D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr