Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53.
The p53 tumor suppressor protein is a critical regulator of cell cycle progression and apoptosis following exposure of cells to DNA damaging agents such as ionizing radiation or anticancer drugs. An important group of anticancer drugs, including compounds such as etoposide and doxorubicin (Adriamycin), interacts with DNA topoisomerase II (topo II), causing the accumulation of enzyme-DNA adducts that ultimately lead to double-strand breaks and cell death via apoptosis. Human topo IIbeta has previously been shown to interact with p53, and we have extended this analysis to show that both topo IIalpha and IIbeta interact with p53 in vivo and in vitro. Furthermore, we show that the regulatory C-terminal basic region of p53 (residues 364-393) is necessary and sufficient for interaction with DNA topo II.
Cowell
I G
IG
School of Biochemistry and Genetics, University of Newcastle, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Okorokov
A L
AL
Cutts
S A
SA
Padget
K
K
Bell
M
M
Milner
J
J
Austin
C A
CA
D017398:Alternative Splicing; D000951:Antigens, Neoplasm; D001665:Binding Sites; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D016296:Mutagenesis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D004250:DNA Topoisomerases, Type II