Polyubiquitin Profile in Down Syndrome and Alzheimer's Disease Brain.

Abstract

Posttranslational modifications (PTMs) of a protein are chemical modifications that play a key role because they regulate almost all cellular events, including gene expression, signal transduction, protein-protein interaction, cell-cell interaction, and communication. Defects in PTMs have been linked to numerous developmental disorders and human diseases, highlighting the importance of PTMs in maintaining normal cellular states. PTMs reversibly or irreversibly alter the structure and properties of proteins through biochemical reactions, thus extending protein function beyond what is dictated by gene transcripts. As analytical approaches have evolved, the biological influences of many types of PTMs have been identified and are routinely analyzed in many systems.Among several types of PTMs, polyubiquitination-addition of ubiquitin (often in the form of polymers) to substrates-governs a variety of biological processes ranging from proteolysis to DNA damage response. The functional flexibility of this modification correlates with the existence of a large number of ubiquitinating enzymes that form distinct ubiquitin polymers, which in turn result in different signals. Thus, the need of specific and sensitive methods for the analysis of the complexity of ubiquitin chain linkage is needed to understand how this structural diversity could translate into various cellular functions. In this section, we described a detailed protocol to enrich polyubiquitinated proteins.