Y. Fujioka et al., MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer, J BIOL CHEM, 276(48), 2001, pp. 45137-45144
The c-myc oncogene product (c-Myc) is a transcription factor that dimerizes
with Max and recognizes the E-box sequence, and it plays key functions in
cell proliferation, differentiation, and apoptosis. We previously showed th
at MM-1 bound to myc box II within the transactivation domain of c-Myc and
repressed the E-box-dependent transcriptional activity of c-Myc. Here we re
port that MM-1 showed features of a tumor suppressor. In an EST data base s
earch for cDNAs homologous to MM-1, we found a frequent substitution of ami
no acid 157 of MM-1, from alanine to arginine (A157R), and the substitution
was observed more in tumor cells than in normal cells. A survey of the A15
7R mutation of MM-1 in 57 cultured cancer cells and 90 tissues from cancer
patients showed that the A157R was present in about 50-60% of leukemia/lymp
homa cells and in more than 75% of squamous cell carcinoma of tongue cancer
. Although both the A157R and the wild-type MM-1 bound to c-Myc, only A157R
lost the activities to repress both the E-box-dependent transcriptional ac
tivity of c-Myc and the myc/ras cooperative transforming activity in rat 3Y
1 cells. Furthermore, the wild-type MM-1, but not A157R, arrested the growt
h of 3Y1 cells. The human MM-1 gene was mapped at chromosome 12q12-12q13, w
here many chromosome abnormalities in cancer cells have been reported. The
results suggest that MM-1 is a novel candidate for a tumor suppressor that
controls the transcriptional activity of c-Myc.