Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a purified ubiquitination system capable of rapidly catalyzing the covalent linkage of polyubiquitin chains onto a model substrate, phosphorylated IkappaBalpha. The initial ubiquitin transfer and subsequent polymerization steps of this reaction require the coordinated action of Cdc34 and the SCF(HOS/beta-TRCP)-ROC1 E3 ligase complex, comprised of four subunits (Skp1, cullin 1 [CUL1], HOS/beta-TRCP, and ROC1). Deletion analysis reveals that the N terminus of CUL1 is both necessary and sufficient for binding Skp1 but is devoid of ROC1-binding activity and, hence, is inactive in catalyzing ubiquitin ligation. Consistent with this, introduction of the N-terminal CUL1 polypeptide into cells blocks the tumor necrosis factor alpha-induced and SCF-mediated degradation of IkappaB by forming catalytically inactive complexes lacking ROC1. In contrast, the C terminus of CUL1 alone interacts with ROC1 through a region containing the cullin consensus domain, to form a complex fully active in supporting ubiquitin polymerization. These results suggest the mode of action of SCF-ROC1, where CUL1 serves as a dual-function molecule that recruits an F-box protein for substrate targeting through Skp1 at its N terminus, while the C terminus of CUL1 binds ROC1 to assemble a core ubiquitin ligase.
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PMID:The SCF(HOS/beta-TRCP)-ROC1 E3 ubiquitin ligase utilizes two distinct domains within CUL1 for substrate targeting and ubiquitin ligation. 1064 23

F-box proteins are essential components of the Skp-cullin-F-box complex (a type of E3 ubiquitin ligase), and participate in cell cycle and immune responses through the ubiquitin proteasome system. F-box protein 39 (FBXO39) belongs to the F-box family, which has been reported to be associated with cancer oncogenesis and progression. The present study aimed to investigate the role of FBXO39 in osteosarcoma (OS) cell proliferation and apoptosis in vitro. It was demonstrated that U-2OS cells exhibited high expression of FBXO39 compared with HOS and SaOS-2 osteosarcoma cells. Thus, knockdown of FBXO39 was performed using lentivirus-mediated short hairpin RNA (shRNA) transfection to validate the effect of FBXO39 in U-2OS cells. Western blotting and RT-qPCR analysis were used to confirm the efficiency of infection by analyzing the expression level of FBXO39. Using Celigo-based cell counting and MTT assays, it was demonstrated that FBXO39 knockdown significantly reduced the rate of cell proliferation compared with control. Caspase 3/7 activity assays and fluorescence-activated cell sorting confirmed the induction of apoptosis in U-2OS cells following FBXO39 knockdown. In conclusion, it was demonstrated that FBXO39 knockdown may significantly inhibit proliferation and promote apoptosis of U-2OS cells. Thus, FBXO39 may serve an important role in OS progression.
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PMID:Knockdown of FBXO39 inhibits proliferation and promotes apoptosis of human osteosarcoma U-2OS cells. 3000 75