Disorders of Protein Biogenesis and Stability

The great diversity of structural conformations available to proteins allows this class of molecules to carry out the vast majority of biochemical functions in the cell. In order to function adequately, proteins must be synthesized, folded/assembled and degraded with great temporal and spatial accuracy. Precise coordination of multiple processes, including ribosome assembly and movement along mRNA, charging and recycling of tRNAs, recruitment and action of molecular chaperones, and tight control of the degradation machinery is essential to create and maintain a stable proteome. It has become recently evident that even slight errors in any of these processes may lead to disease states. Accordingly, increasing numbers of human diseases have been identified that are due to mutations in genes encoding proteins involved in this so-called “protein quality control”. Since these processes are essential for the production and maintenance of the entire proteome of the cell, the deleterious effects of these mutations often extend far beyond the faulty gene. This review provides an overview of human disorders caused by defects in mechanisms underlying protein biogenesis and stability.