tailieunhanh - Báo cáo khoa học: 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

NBR1(named as next toBRCA1) was originally cloned as a candidate gene for the ovarian cancer antigen CA125, using expression cloning with the anti-CA125 Ig, has been of interest due to its position close toBRCA1, although no involvement in breast or ovarian cancer has been demonstrated. Recently, the antigen CA125 has been cloned, and identi®ed as a new mucin, MUC16, entirely di erent from NBR1. | Eur. J. Biochem. 269 538-545 2002 FEBS 2002 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 Caroline Whitehouse1 Julie Chambers Kathy Howe1 Martyn Cobourne2 Paul Sharpe2 and Ellen Solomon1 1 Division of Medical and Molecular Genetics and department of Craniofacial Development GKT School of Medicine Guy s Hospital London UK 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 PKCf 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. Keywords ZZ zinc binding domain OPR domain UBA domain CIB FEZ1. The human NBR1

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