title: Downregulation of ubiquitin level via knockdown of polyubiquitin gene Ubb as potential cancer therapeutic intervention.
abstract: Ubiquitin is involved in almost every cellular process, and it is also known to be a stress-inducible protein. Based on previous reports that many types of cancer display an elevated level of ubiquitin, we hypothesized that this increased amount of ubiquitin is essential for the growth of cancer cells and that, consequently, the downregulation of ubiquitin may be a potential anti-cancer treatment. We first found that the level of ubiquitin can be effectively downregulated via knockdown of a polyubiquitin gene, Ubb, with siRNA (Ubb-KD) and then demonstrated its anti-cancer effects in several cancer cell lines and xenograft mice. Ubb-KD resulted in the attenuation of TNFα-induced NF-κB activation, the stabilization of the tumor suppressor p53, and stress-sensitization. Taken together, downregulation of ubiquitin through Ubb-KD is a potential anti-cancer treatment by inhibiting ubiquitination at multiple sites related to oncogenic pathways and by weakening the ability of cancer cells to overcome increased stress.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science & Technology (GIST), Gwangju 500-712, Republic of Korea.
authors.forename: Choongseob
authors.initials: C
authors.lastname: Oh
authors.forename: Soonyong
authors.initials: S
authors.lastname: Park
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Yung Joon
authors.initials: YJ
authors.lastname: Yoo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D025821:Polyubiquitin / Q000235:genetics* / Q000378:metabolism*; D059748:Proteolysis; D034622:RNA Interference; D047368:Tumor Burden / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025801:Ubiquitin / Q000235:genetics* / Q000378:metabolism*; D054875:Ubiquitination; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C479419:UBB protein, human; D025801:Ubiquitin; D025821:Polyubiquitin
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