The ubiquitin-interacting motif of 26S proteasome subunit S5a induces A549 lung cancer cell death.
The subunit S5a is a key component for the recruitment of ubiquitinated substrates to the 26S proteasome. When the full-length S5a, the N-terminal half of S5a (S5aN) containing the von Willebrand A (vWA) domain, and the C-terminal half of S5a (S5aC) containing two ubiquitin(Ub)-interacting motifs (UIMs) were ectopically expressed in HEK293 cells, Ub-conjugates accumulated most prominently in S5aC-expressing cells. In addition, S5aC induced A549 lung cancer cell death but not non-cancer BEAS-2B cell death. Similar effects were observed using only S5a-UIMs. Our data therefore suggest that S5a-UIMs can be used as upstream inhibitors of the proteasome pathway.
Elangovan
Muthukumar
M
Department of Life Science, Gwangju Institute of Science & Technology (GIST), 1 Oryong-dong Buk-ku, Gwangju, Republic of Korea.
Choi
Eun Soo
ES
Jang
Bong Geom
BG
Kim
Mi Sun
MS
Yoo
Yung Joon
YJ
D016923:Cell Death; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D025801:Ubiquitin / Q000378:metabolism*
C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease