The ubiquitin-interacting motifs of S5a as a unique upstream inhibitor of the 26S proteasome.
It has been demonstrated that ubiquitin-conjugated proteins were accumulated by ectopically-expressed S5a as well as the ubiquitin-interacting motifs of S5a (S5a-UIMs). In this study, we further found that free S5a-UIMs stabilized only a subset of proteasomal substrates including p53, c-Fos, c-Jun, and p27 but not beta-catenin, p15, and ornithine decarboxylase. Both S5a-UIMs and epoxomicin inhibited the proliferation of A549 lung cancer cells but arrest at the different stages of cell cycle. Together, our results suggest a potential role of S5a-UIMs as an upstream proteasomal inhibitor by blocking the subset of substrates from delivery to the 26S proteasome.
Elangovan
Muthukumar
M
Department of Life Science, Gwangju Institute of Science & Technology, Gwangju 500-712, Republic of Korea.
Shin
Dong Yeon
DY
Yoo
Yung Joon
YJ
D020816:Amino Acid Motifs / Q000235:genetics; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
D000970:Antineoplastic Agents; D009842:Oligopeptides; C498506:PSMD4 protein, human; D061988:Proteasome Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C078846:epoxomicin