Regulation Of Lens Fiber Membrane Gene Expression

National Eye Institute

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Abstract

This project studies the regulation of expression of genes encoding lens fiber membrane channel proteins, which are essential for maintaining the transparency and correct refractive index of the lens. We are presently focusing on the regulation of expression of the gene encoding MIP, the major intrinsic protein of the lens fiber membrane that is specifically expressed in the ocular lens fibers and belongs to an ancient family of transmembrane channel proteins. We have cloned the MIP gene from mouse and human. We are focusing on the characterization of MIP promoter regulatory elements conserved in mouse and human by using the yeast one-hybrid system. We are also studying the expression of the transcription factor AP2 alpha that interacts with promoter elements of the MIP gene. We found that the transcription factor AP2 alpha is expressed in the lens epithelia but not in the lens fibers. We have characterized several alternative spliced variants of the AP2 alpha gene expressed in the lens. Some of these variants may function as activators or repressors. Present studies focus on the interaction of the activation domain of the transcription factor AP2 alpha with other proteins. To this end we have screened phage display libraries with peptides corresponding to regions of the AP2 alpha transactivation domain. We have isolated from the phage display library several cDNAs encoding proteins that interact with AP2 alpha. One of them encodes a protein that also interacts with the retinoblastoma protein. Further characterization of these interactions may provide insights into the functional implications of these protein-protein interactions.