Distamycin inhibits the binding of a nuclear factor to the -278/-256 upstream sequence of the human HLA-DR alpha gene.
In this study we analyse the effects of the anti-tumor compound distamycin on the binding of nuclear factor(s) to a synthetic oligonucleotide (GTATA/IFN-gamma) mimicking a putative regulatory region of the human HLA-DR alpha gene. This region contains the sequence (GTATA), that is required for nuclear protein binding and is likely to interact with distamycin. The present results, by showing that distamycin inhibits the interaction between nuclear factors and the GTATA/IFN-gamma oligonucleotide, suggest that distamycin might alter the binding of transacting factors to cis-elements containing AT/TA sequences. Alterations of nuclear protein binding to specific target sequences could be one of the molecular mechanism(s) by which distamycin exerts its antiproliferative activity on living cells.
Gambari
R
R
Istituto di Chimica Biologica, Università di Ferrara, Italy.
Barbieri
R
R
Nastruzzi
C
C
Chiorboli
V
V
Feriotto
G
G
Natali
P G
PG
Giacomini
P
P
Arcamone
F
F
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D004214:Distamycins / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism; D011401:Promoter Regions, Genetic
D000970:Antineoplastic Agents; D004214:Distamycins; D006684:HLA-DR Antigens; D009687:Nuclear Proteins; D009841:Oligonucleotides