Borrelidin inhibits a cyclin-dependent kinase (CDK), Cdc28/Cln2, of Saccharomyces cerevisiae.
We identified borrrelidin, a member of macrolide antibiotic, as an inhibitor of a cyclin-dependent kinase of the budding yeast, Cdc28/Cln2. A 50% inhibition concentration (IC50) of borrelidin for Cdc28/Cln2 was 24 microM. In addition, borrelidin arrests both haploid and diploid cells in G1 phase at the point indistinguishable from that of alpha-mating pheromone, at concentrations not affecting the gross protein synthesis. Although the inhibition of CDK activity may not be a solo cause of the G1 arrest, our results indicate that borrelidin is a potential lead compound for developing novel CDK inhibitors of higher eukaryotes.
Tsuchiya
E
E
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Japan. stsuchi@hiroshima-u.ac.jp
Yukawa
M
M
Miyakawa
T
T
Kimura
K I
KI
Takahashi
H
H
D017489:CDC28 Protein Kinase, S cerevisiae / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D005656:Fungal Proteins / Q000096:biosynthesis / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D020128:Inhibitory Concentration 50; D000072235:Mating Factor; D010455:Peptides / Q000187:drug effects / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology
D004791:Enzyme Inhibitors; D005233:Fatty Alcohols; D005656:Fungal Proteins; D010455:Peptides; D000072235:Mating Factor; C005066:borrelidin; D017489:CDC28 Protein Kinase, S cerevisiae