Open AccessMEK‐ERK is involved in SUMO‐1 foci formation on apoptosis
Author(s) -
UtsuboKuniyoshi Ryoko,
Terui Yasuhito,
Mishima Yuko,
Rokudai Akiko,
Mishima Yuji,
Sugimura Natsuhiko,
Kojima Kiyotsugu,
Sonoda Yoshiko,
Kasahara Tadashi,
Hatake Kiyohiko
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00422.x
Subject(s) - sumo protein , k562 cells , green fluorescent protein , apoptosis , mapk/erk pathway , chemistry , microbiology and biotechnology , nuclear export signal , small interfering rna , sumo enzymes , biology , transfection , signal transduction , cell nucleus , ubiquitin , biochemistry , gene , cytoplasm
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. ( Cancer Sci 2007; 98: 569–576)