Girolline, an antitumor compound isolated from a sponge, induces G2/M cell cycle arrest and accumulation of polyubiquitinated p53.
Girolline, an antitumor compound isolated from a sponge, has been reported to inhibit the termination step of protein synthesis in vivo. In this study, we found that girolline induced G2/M cell cycle arrest in several tumor cell lines. Immunochemical analysis revealed that polyubiquitinated p53 was accumulated in girolline-treated cells, while other polyubiquitinated cellular proteins were not accumulated, indicating that the effect of girolline is specific for p53. On the other hand, girolline did not inhibit proteasome activity in vitro, and accumulation of polyubiquitinated p53 was scarcely detected in the presence of leptomycin B, an inhibitor of nuclear export. Based on the above findings, we propose that girolline affects the step of recruitment of polyubiquitinated p53 to the proteasome.
Tsukamoto
Sachiko
S
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan. sachiko@p.kanazawa-u.ac.jp
Yamashita
Katsumi
K
Tane
Kazuhiro
K
Kizu
Ryoichi
R
Ohta
Tomihisa
T
Matsunaga
Shigeki
S
Fusetani
Nobuhiro
N
Kawahara
Hiroyuki
H
Yokosawa
Hideyoshi
H
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D047089:Axinella; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D016195:G2 Phase / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000302:isolation & purification / Q000494:pharmacology*; D025821:Polyubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000970:Antineoplastic Agents; D007093:Imidazoles; D016159:Tumor Suppressor Protein p53; C526558:girolline; D025821:Polyubiquitin