title: Rlim, an E3 ubiquitin ligase, influences the stability of Stathmin protein in human osteosarcoma cells.
abstract: Stathmin is an oncoprotein and is expressed at high levels in a wide variety of human malignancies, which plays important roles in maintenance of malignant phenotypes. The regulation of Stathmin gene overexpression has been wildly explored, but the exact mechanism still needs to be elucidated. It is believed that regulation of an oncogene protein abundance through post-translational modifications is essential for maintenance of malignant phenotypes. Here we identified the Rlim, a Ring H2 zinc finger protein with intrinsic ubiquitin ligase activity, as a Stathmin-interacting protein that could increase Stathmin turnover through binding with this targeted protein and then induce its degradation by proteasome in a ubiquitin-dependent manner. Inhibition of endogenous Rlim expression by siRNA could increase the level of Stathmin protein, which further led to cell proliferation and cell cycle changes in human osteosarcoma cell lines. On the other hand, forced overexpression of Rlim could decrease the level of Stathmin protein. These results demonstrate that Rlim is involved in the negative regulation of Stathmin protein level through physical interaction and ubiquitin-mediated proteolysis. Hence, Rlim is a novel regulator of Stathmin protein in a ubiquitin-dependent manner, and represents a new pathway for malignant phenotype turnover by modulating the level of Stathmin protein in human osteosarcomas.
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Ophthalmology, Xi'an No. 4 Hospital, Xi'an, China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Min
authors.initials: M
authors.lastname: Long
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Microbiology & Immunology, Emory University School of Medicine, Atlanta, USA.
authors.forename: Chinglai
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: tddk01@126.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: td_zhz@163.com.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D034622:RNA Interference; D034741:RNA, Small Interfering; D050777:Stathmin / Q000096:biosynthesis / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D034741:RNA, Small Interfering; C493995:STMN1 protein, human; D050777:Stathmin; D025801:Ubiquitin; C492370:RLIM protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Degradation; E3 ubiquitin-protein ligase; Rlim; Stathmin