Fig. 5: SEC23B interacts with proteins related to the cellular stress response pathway.

A Pathway analysis of SEC23B-interacting proteins in Nthy-SEC23B-WT and Nthy-SEC23B-V594G cells with and without MG132 treatment. EIF2 eukaryotic initiation factor 2 signalling, UPR unfolded protein response, UBIQ protein ubiquitination pathway, Sqrt square root, MUT SEC23B-V594G. B Validation of the SEC23B–UBA52 interaction using immunoprecipitation of EGFP-tagged SEC23B in Nthy-SEC23B-WT and Nthy-SEC23B-V594G cells followed by immunoblotting using the UBA52 antibody. Nthy-EGFP cell line and normal rabbit IgG are used as negative controls. UBA52 protein levels are normalized to SEC23B-EGFP pulldown within each genotype and quantification values are relative to wild-type. Mutant SEC23B shows increased binding to UBA52. C SEC23B and UBA52 protein levels in patient-derived SEC23B wild-type and p.Val594Gly mutant lymphoblastoid cell line (LBL) pools with and without treatment with the ER stress-inducing agent Thapsigargin (600 nM, 5 days). Each genotypic group includes 5 LBLs with either wild-type or p.V594G mutant SEC23B, respectively (see “Materials and methods”). D Proposed model of how SEC23B, irrespective of mutation status, could be playing multiple unexplored roles in the cellular stress response pathway. SEC23B–UBA52 cross-talk represents one proof-of-principle example.