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We isolated two novel 14-3-3 binding proteins using 14-3-3fas bait in a yeast two-hybrid screen of a human brain cDNA library. One of these encoded the C-terminus of a neural specific armadillo-repeat protein, d-catenin (neural plakophilin-related arm-repeat protein or neurojungin). d-Catenin from brain lysates was retained on a 14-3-3 affinity column. | iFEBS Journal Novel brain 14-3-3 interacting proteins involved in neurodegenerative disease Shaun Mackie and Alastair Aitken University of Edinburgh Schoolof Biomedicaland ClinicalLaboratory Sciences Edinburgh Scotland UK Keywords 14-3-3 S-catenin IRSp53 neurodegenerative diseases yeast two-hybrid Correspondence A. Aitken University of Edinburgh Schoolof Biomedical and Clinical Laboratory Sciences George Square Edinburgh EH8 9XD Scotland UK Fax 44 131 6503725 Tel 44 131 6503721 E-mail alastair.aitken@ed.ac.uk Present address University of Edinburgh Psychiatric Genetics Section Medical Genetics Section Western General Hospital Edinburgh Scotland We isolated two novel 14-3-3 binding proteins using 14-3-3 f as bait in a yeast two-hybrid screen of a human brain cDNA library. One of these encoded the C-terminus of a neural specific armadillo-repeat protein S-catenin neural plakophilin-related arm-repeat protein or neurojungin . S-Catenin from brain lysates was retained on a 14-3-3 affinity column. Mutation of serine 1072 in the human protein and serine 1094 in the equivalent site in the mouse homologue in a consensus binding motif for 14-33 abolished 14-3-3 binding to S-catenin in vitro and in transfected cells. S-catenin binds to presenilin-1 encoded by the gene most commonly mutated in familial Alzheimer s disease. The other clone was identified as the insulin receptor tyrosine kinase substrate protein of 53 kDa IRSp53 . Human IRSp53 interacts with the gene product implicated in dentatoru-bral-pallidoluysian atrophy an autosomal recessive disorder associated with glutamine repeat expansion of atrophin-1. Received 31 January 2005 revised 13 May 2005 accepted 22 June 2005 doi 10.1111 j.1742-4658.2005.04832.x Dimeric 14-3-3 proteins have important functions in diverse biological processes 1-3 . An optimal motif for 14-3-3 binding was identified as R S XpSXP 4 where Sp is phosphoserine. This was later refined to include a second motif mode 2 RXXXpSXP 5 . A number of .
