Scholefield, JanineHenriques, RSavulescu, AFFontan, EBoucharlat, ALaplantine, ESmahi, AIsrael, AAgou, FMhlanga, Musa2017-02-232017-02-232016-09Scholefield, J., Henriques, R., Savulescu, A.F., Fontan, E., Boucharlat, A., Laplantine, E., Smahi, A. Israel, A., Agou, F. and Mhlanga, M.M. 2016. Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti. Nature Communications, 7(12692)2041-1723http://www.nature.com/articles/ncomms12629http://hdl.handle.net/10204/8960Copyright: 2016 Nature Publishing GroupThe NF- B pathway has critical roles in cancer, immunity and inflammatory responses. Understanding the mechanism(s) by which mutations in genes involved in the pathway cause disease has provided valuable insight into its regulation, yet many aspects remain unexplained. Several lines of evidence have led to the hypothesis that the regulatory/sensor protein NEMO acts as a biological binary switch. This hypothesis depends on the formation of a higher-order structure, which has yet to be identified using traditional molecular techniques. Here we use super-resolution microscopy to reveal the existence of higher-order NEMO lattice structures dependent on the presence of polyubiquitin chains before NF- B activation. Such structures may permit proximity-based trans-autophosphorylation, leading to cooperative activation of the signalling cascade. We further show that NF- B activation results in modification of these structures. Finally, we demonstrate that these structures are abrogated in cells derived from incontinentia pigmenti patients.enNEMO lattice structureNF- B pathwayIncontinentia pigmentiArticleScholefield, J., Henriques, R., Savulescu, A., Fontan, E., Boucharlat, A., Laplantine, E., ... Mhlanga, M. (2016). Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti. http://hdl.handle.net/10204/8960Scholefield, Janine, R Henriques, AF Savulescu, E Fontan, A Boucharlat, E Laplantine, A Smahi, A Israel, F Agou, and Musa Mhlanga "Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti." (2016) http://hdl.handle.net/10204/8960Scholefield J, Henriques R, Savulescu A, Fontan E, Boucharlat A, Laplantine E, et al. Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti. 2016; http://hdl.handle.net/10204/8960.TY - Article AU - Scholefield, Janine AU - Henriques, R AU - Savulescu, AF AU - Fontan, E AU - Boucharlat, A AU - Laplantine, E AU - Smahi, A AU - Israel, A AU - Agou, F AU - Mhlanga, Musa AB - The NF- B pathway has critical roles in cancer, immunity and inflammatory responses. Understanding the mechanism(s) by which mutations in genes involved in the pathway cause disease has provided valuable insight into its regulation, yet many aspects remain unexplained. Several lines of evidence have led to the hypothesis that the regulatory/sensor protein NEMO acts as a biological binary switch. This hypothesis depends on the formation of a higher-order structure, which has yet to be identified using traditional molecular techniques. Here we use super-resolution microscopy to reveal the existence of higher-order NEMO lattice structures dependent on the presence of polyubiquitin chains before NF- B activation. Such structures may permit proximity-based trans-autophosphorylation, leading to cooperative activation of the signalling cascade. We further show that NF- B activation results in modification of these structures. Finally, we demonstrate that these structures are abrogated in cells derived from incontinentia pigmenti patients. DA - 2016-09 DB - ResearchSpace DP - CSIR KW - NEMO lattice structure KW - NF- B pathway KW - Incontinentia pigmenti LK - https://researchspace.csir.co.za PY - 2016 SM - 2041-1723 T1 - Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti TI - Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti UR - http://hdl.handle.net/10204/8960 ER -