Dnacin A1 and dnacin B1 are antitumor antibiotics that inhibit cdc25B phosphatase activity.
The p80cdc25 protein is a protein phosphatase directly involved in p34cdc2 protein kinase activation by dephosphorylation. The cdc25B gene is one of three human cdc25 homologs which can complement the temperature-sensitive cdc25 mutation of Schizosaccharomyces pombe, and is expressed a high levels in human cell lines, particularly in some cancer cells. A fusion protein of glutathione-S-transferase (GST) and the catalytic domain of cdc25B protein was constructed and found to retain phosphatase activity in the manner of a p80cdc25 phosphatase by using a chromogenic substrate, p-nitrophenylphosphate. Two benzoquinoid antitumor compounds, dnacin A1 and dnacin B1, inhibited phosphatase activity in a non-competitive manner.
Horiguchi
T
T
Discovery Research Laboratories II, Takeda Chemical Industries, Ltd, Osaka, Japan.
Nishi
K
K
Hakoda
S
S
Tanida
S
S
Nagata
A
A
Okayama
H
H
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D020687:cdc25 Phosphatases
D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; D011506:Proteins; D011809:Quinones; C030786:dnacins; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases