Now showing items 1-8 of 8

    • Binding to an Unusual Inactive Kinase Conformation by Highly Selective Inhibitors of Inositol-Requiring Enzyme 1α Kinase-Endoribonuclease. 

      Colombano, G; Caldwell, JJ; Matthews, TP; Bhatia, C; Joshi, A; McHardy, T; Mok, NY; Newbatt, Y; Pickard, L; Strover, J; Hedayat, S; Walton, MI; Myers, SM; Jones, AM; Saville, H; McAndrew, C; Burke, R; Eccles, SA; Davies, FE; Bayliss, R; Collins, I (2019-03-05)
      A series of imidazo[1,2- b]pyridazin-8-amine kinase inhibitors were discovered to allosterically inhibit the endoribonuclease function of the dual kinase-endoribonuclease inositol-requiring enzyme 1α (IRE1α), a key component ...
    • Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells. 

      Nikkilä, J; Kumar, R; Campbell, J; Brandsma, I; Pemberton, HN; Wallberg, F; Nagy, K; Scheer, I; Vertessy, BG; Serebrenik, AA; Monni, V; Harris, RS; Pettitt, SJ; Ashworth, A; Lord, CJ (2017-06)
      Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 status on ...
    • Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation. 

      van Weverwijk, A; Koundouros, N; Iravani, M; Ashenden, M; Gao, Q; Poulogiannis, G; Jungwirth, U; Isacke, CM (2019-06-20)
      The different stages of the metastatic cascade present distinct metabolic challenges to tumour cells and an altered tumour metabolism associated with successful metastatic colonisation provides a therapeutic vulnerability ...
    • Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's Cytotoxic Potential. 

      Feltham, R; Jamal, K; Tenev, T; Liccardi, G; Jaco, I; Domingues, CM; Morris, O; John, SW; Annibaldi, A; Widya, M; Kearney, CJ; Clancy, D; Elliott, PR; Glatter, T; Qiao, Q; Thompson, AJ; Nesvizhskii, A; Schmidt, A; Komander, D; Wu, H; Martin, S; Meier, P (2018-04)
      Tumor necrosis factor (TNF) is an inflammatory cytokine that can signal cell survival or cell death. The mechanisms that switch between these distinct outcomes remain poorly defined. Here, we show that the E3 ubiquitin ...
    • SUMO-mediated regulation of NLRP3 modulates inflammasome activity. 

      Barry, R; John, SW; Liccardi, G; Tenev, T; Jaco, I; Chen, C-H; Choi, J; Kasperkiewicz, P; Fernandes-Alnemri, T; Alnemri, E; Drag, M; Chen, Y; Meier, P (2018-08)
      The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is ...
    • The cylindromatosis gene product, CYLD, interacts with MIB2 to regulate notch signalling. 

      Rajan, N; Elliott, RJR; Smith, A; Sinclair, N; Swift, S; Lord, CJ; Ashworth, A (2014-12)
      CYLD, an ubiquitin hydrolase, has an expanding repertoire of regulatory roles in cell signalling and is dysregulated in a number of cancers. To dissect CYLD function we used a proteomics approach to identify CYLD interacting ...
    • Ubiquitin-Mediated Regulation of RIPK1 Kinase Activity Independent of IKK and MK2. 

      Annibaldi, A; Wicky John, S; Vanden Berghe, T; Swatek, KN; Ruan, J; Liccardi, G; Bianchi, K; Elliott, PR; Choi, SM; Van Coillie, S; Bertin, J; Wu, H; Komander, D; Vandenabeele, P; Silke, J; Meier, P (2018-02)
      Tumor necrosis factor (TNF) can drive inflammation, cell survival, and death. While ubiquitylation-, phosphorylation-, and nuclear factor κB (NF-κB)-dependent checkpoints suppress the cytotoxic potential of TNF, it remains ...
    • Ubiquitylation of MLKL at lysine 219 positively regulates necroptosis-induced tissue injury and pathogen clearance. 

      Garcia, LR; Tenev, T; Newman, R; Haich, RO; Liccardi, G; John, SW; Annibaldi, A; Yu, L; Pardo, M; Young, SN; Fitzgibbon, C; Fernando, W; Guppy, N; Kim, H; Liang, L-Y; Lucet, IS; Kueh, A; Roxanis, I; Gazinska, P; Sims, M; Smyth, T; Ward, G; Bertin, J; Beal, AM; Geddes, B; Choudhary, JS; Murphy, JM; Aurelia Ball, K; Upton, JW; Meier, P (2021-06-07)
      Necroptosis is a lytic, inflammatory form of cell death that not only contributes to pathogen clearance but can also lead to disease pathogenesis. Necroptosis is triggered by RIPK3-mediated phosphorylation of MLKL, which ...