title: NBR1 interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB) and shows developmentally restricted expression in the neural tube.
abstract: NBR1 (named as next to BRCA1) was originally cloned as a candidate gene for the ovarian cancer antigen CA125, using expression cloning with the anti-CA125 Ig, OC125. NBR1 has been of interest due to its position close to BRCA1, although no involvement in breast or ovarian cancer has been demonstrated. Recently, the antigen CA125 has been cloned, and identified as a new mucin, MUC16, entirely different from NBR1. The function of NBR1 remains unknown. To investigate its function, a yeast two-hybrid study was performed to identify interacting protein partners that may reflect a biological role for this protein. Here, we show that NBR1 interacts with two proteins; fasciculation and elongation protein zeta-1 (FEZ1), a PKCzeta interacting protein, and calcium and integrin binding protein (CIB), which is associated with polo-like kinases Fnk/Snk and the Alzheimer's disease presenilin 2 protein. Co-transfection of FEZ1 and NBR1 showed overlapping localization in the cytoplasm, whereas coexpression of NBR1 and CIB resulted in a shift of CIB protein expression from the nucleus to the perinuclear compartment. FEZ1 is highly expressed in the brain and in situ hybridization analysis of Nbr1 showed that its expression is also regulated in the murine brain during development. These data suggest that NBR1 may function, through interaction with CIB and FEZ1 in cell signalling pathways, with a developmentally restricted expression suggesting a possible role in neural development.
authors.affiliation: Division of Medical and Molecular Genetics, and Department of Craniofacial Development, GKT School of Medicine, Guy's Hospital, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Whitehouse
authors.forename: Julie
authors.initials: J
authors.lastname: Chambers
authors.forename: Kathy
authors.initials: K
authors.lastname: Howe
authors.forename: Martyn
authors.initials: M
authors.lastname: Cobourne
authors.forename: Paul
authors.initials: P
authors.lastname: Sharpe
authors.forename: Ellen
authors.initials: E
authors.lastname: Solomon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009420:Nervous System / Q000196:embryology / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C491605:Cib1 protein, mouse; D004268:DNA-Binding Proteins; C528597:FEZ1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C118711:LZTS1 protein, human; C549756:NBR1 protein, human; C486326:Nbr1 protein, mouse; D009419:Nerve Tissue Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins