MEK-ERK is involved in SUMO-1 foci formation on apoptosis.
Small ubiquitin-related modifier (SUMO) modification appears to regulate the activity, intracellular localization, and stability of the targeted proteins. To explore the relationship among sumoylation, antitumor reagent, and apoptosis, we treated green fluorescence protein (GFP)-SUMO-1-overexpressed K562 cells (K562/GFP-SUMO-1) with mitoxantrone (MIT) as an antitumor reagent. By the treatment with MIT, GFP-SUMO-1 formed foci in nuclei. While by the treatment with a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), GFP-SUMO-1 located homogeneously in nuclei. When K562/GFP-SUMO-1 cells were treated with TPA plus MIT, GFP-SUMO-1 foci became larger and apoptosis was induced more than with MIT alone. The apoptosis induced by TPA plus MIT was prevented by blockage of GFP-SUMO-1 foci by small interfering RNA (siRNA) against SUMO-1. The formation of GFP-SUMO-1 foci was reduced by a MEK inhibitor U0126 or a nuclear export inhibitor leptomycin B, and endogenous SUMO-1 foci were reduced in K562 cells expressing the dominant-negative MEK1 mutant. These results suggest that the formation of SUMO-1 foci is regulated by the MEK-ERK pathway and may induce apoptosis.
Utsubo-Kuniyoshi
Ryoko
R
Division of Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan.
Terui
Yasuhito
Y
Mishima
Yuko
Y
Rokudai
Akiko
A
Mishima
Yuji
Y
Sugimura
Natsuhiko
N
Kojima
Kiyotsugu
K
Sonoda
Yoshiko
Y
Kasahara
Tadashi
T
Hatake
Kiyohiko
K
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D002070:Butadienes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D025842:SUMO-1 Protein / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D002070:Butadienes; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; C485425:LAMTOR3 protein, human; D009570:Nitriles; D034741:RNA, Small Interfering; D025842:SUMO-1 Protein; C113580:U 0126; D008942:Mitoxantrone; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate; C038753:leptomycin B