s-Myc acts as a transcriptional activator and its sequence-specific DNA binding is required for induction of programmed cell death in glioma cells.
We previously reported that s-Myc expression effectively induces programmed cell death (PCD) by apoptosis in glioma cells that express only mutated p53. To determine the molecular mechanism of s-Myc-induced PCD, we examined the correlation between transcriptional activation of s-Myc and its ability to induce PCD. Using a reporter plasmid having an upstream promoter region containing four repeats of the hexanucleotide CACGTG, we found that s-Myc can activate transcription of a reporter gene from this plasmid. Two mutated forms of s-Myc protein, s-MycCKII and s-MycmBR, were created. While s-MycCKII whose casein kinase (CK) II cognate sequence was restored in the internal acidic domain activated transcription as efficiently as wild-type s-Myc and induced PCD in glioma cells, s-MycmBR having a mutated basic region unable to bind the CACGTG motif did not. These findings suggest that transactivation activity of s-Myc through sequence-specific DNA binding may be indispensable for induction of PCD but that lack of a CK-II cognate sequence in the internal acidic domain may have little effect on these functions of s-Myc.
Kitanaka
C
C
Division of Biophysics, National Cancer Center Research Institute.
Sugiyama
A
A
Kanazu
S
S
Miyagi
Y
Y
Mishima
K
K
Asai
A
A
Kuchino
Y
Y