Interaction of MCC2, a novel homologue of MCC tumor suppressor, with PDZ-domain protein AIE-75

AIE-75 is a protein identified as an autoantigen in patients with autoimmun e enteropathy and as a colon cancer-related antigen. It has recently been a ssigned to be a causative gene for Usher type 1C congenital syndromic heari ng loss. The novel protein has three PSD-95/D1g/ ZO-1 (PDZ) protein-protein interaction domains and is therefore implicated to function as a molecular anchor or sorter. We have identified a novel protein that binds to AIE-75 by yeast two-hybrid screening. The protein has a high homology to the tumor suppressor MCC (mutated in colon cancer; or MCC1 hereafter) and was named MCC2. MCC2 protein binds the first PDZ domain of AIE-75 with its C-terminal amino acids -DTFL. Since the MCC1 does not bind to AIE-75 and the MCC2 dis plays different expression patterns in various organs compared to MCC1, the y appear to play distinct roles in cells. The MCC2 gene is located on chrom osome 19p13 in the vicinity of APCL gene, while MCC1 maps near to APC tumor suppressor gene. Because of negative expression of MCC2 in a panel of canc er cell-lines compared to the corresponding normal tissues, we suggest that further study is necessary to investigate a possible role of MCC2 as a tum or suppressor. (C) 2001 Elsevier Science B.V. All rights reserved.