PDZK1, a novel PDZ domain-containing protein up-regulated in carcinomas and mapped to chromosome 1q21, interacts with cMOAT (MRP2), the multidrug resistance-associated protein

We recently reported the isolation and partial characterization of two nove l proteins, MAP17 and PDZK1. Using in situ hybridization, we demonstrated t hat MAP17 and PDZK1 nRNAs are markedly up-regulated in human carcinomas. PD ZK1, originally isolated as a protein interacting with MAP17, contains four PDZ protein-interaction domains and could potentially interact with as man y as four target proteins. In this paper, we confirm the overexpression of PDZK1 in human carcinomas using a specific antibody and demonstrate the loc alization of the PDZK1 gene to human chromosome 1q21, a region frequently a ltered in neoplastic conditions. Using the yeast two-hybrid system, we have also determined that PDZK1 interacts with the carboxy-terminal portion of cMOAT (MRP2), the canalicular multispecific organic anion transporter assoc iated with multidrug resistance. This is of particular interest because pro teins containing PDZ domains are involved in the clustering and signaling p athways of membrane-associated proteins, including ion channels. Therefore, the protein cluster formed by the association of cMOAT, PDZK1, and MAP17 c ould play an important role in the cellular mechanisms associated with mult idrug resistance, and PDZK1 may represent a new target in cancer cells resi stant to chemotherapeutic agents.