Chibby interacts with NBPF1 and clusterin, two candidate tumor suppressors linked to neuroblastoma.
The NBPF genes are members of a gene family that underwent a remarkable increase in their copy number during recent primate evolution. The NBPF proteins contain 5 to 40 copies of a domain known as the NBPF repeat or DUF1220. Very little is known about the function of these domains or about the NBPF proteins. We performed a yeast two-hybrid screening with the aminoterminal domain of NBPF11 and found that Chibby, a documented repressor of Wnt signaling, interacts with multiple NBPF proteins. More specifically, a coiled-coil region in the NBPF proteins interacts with the coiled-coil domain in the carboxyterminal region of Chibby. Nonetheless, this interaction did not influence the repressor function of Chibby in a TOPFLASH reporter assay. Using Chibby as bait in a new yeast two-hybrid screening, we identified clusterin as a binding protein. Chibby and clusterin were co-immunoprecipitated with NBPF1, suggesting the formation of a tri-molecular complex. Although we have not pinpointed the role of these mutual interactions, the possible formation of a macromolecular complex of three candidate tumor suppressor proteins, including the enigmatic NBPF1, points at important functional implications.
Vandepoele
Karl
K
Department for Molecular Biomedical Research, VIB, Ghent, Belgium. Karl.Vandepoele@DMBR.VIB-UGent.be
Staes
Katrien
K
Andries
Vanessa
V
van Roy
Frans
F
D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D051152:Clusterin / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism / Q000502:physiology
C473750:CBY1 protein, human; C495242:CLU protein, human; D002352:Carrier Proteins; D051152:Clusterin; C548899:NBPF1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins