title: Spy1 induces de-ubiquitinating of RIP1 arrest and confers glioblastoma's resistance to tumor necrosis factor (TNF-α)-induced apoptosis through suppressing the association of CLIPR-59 and CYLD.
abstract: Glioblastoma multiforme (GBM), a grade-IV glioma, is resistant to TNF-α induced apoptosis. CLIPR-59 modulates ubiquitination of RIP1, thus promoting Caspase-8 activation to induce apoptosis by TNF-α. Here we reported that CLIPR-59 was down-regulated in GBM cells and high-grade glioma tumor samples, which was associated with decreased cancer-free survival. In GBM cells, CLIPR-59 interacts with Spy1, resulting in its decreased association with CYLD, a de-ubiquitinating enzyme. Moreover, experimental reduction of Spy1 levels decreased GBM cells viability, while increased the lysine-63-dependent de-ubiquitinating activity of RIP1 via enhancing the binding ability of CLIPR-59 and CYLD in GBM, thus promoting Caspase-8 and Caspase-3 activation to induce apoptosis by TNF-α. These findings have identified a novel Spy1-CLIPR-59 interplay in GBM cell's resistance to TNF-α-induced apoptosis revealing a potential target in the intervention of malignant brain tumors.
authors.affiliation: a Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target; Nantong University ; Nantong , Jiangsu , PR China.
authors.forename: Zongmei
authors.initials: Z
authors.lastname: Ding
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.forename: Donglin
authors.initials: D
authors.lastname: Wang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Cui
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.forename: Xianting
authors.initials: X
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D000074749:Deubiquitinating Enzyme CYLD; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects / Q000502:physiology
chemical_list: C119724:AGFG1 protein, human; C449670:CLIP3 protein, human; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; C486530:SPDYA protein, human; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
keywords: CLIPR-59; CLIPR-59, CLIP-170-related 59 kDa protein; FADD, Fas-associated protein with death domain; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GBM glioblastoma multiforme; Glioma; RIP1; RIP1, receptor-interacting protein 1; Spy1; Spy1, speedy inducer of meiotic maturation; TNF-α; TNFR1, TNF-receptor-type 1; TRADD, TNF receptor-associated death domain protein; apoptosis