Protein HomeostasisFolding proteins and maintaining the protein-protein interaction networks

Launched February 2012 Updated October 2014 28 lectures
Prof. Walid A. Houry
University of Toronto, Canada

Protein homeostasis refers to a highly complex and interconnected set of processes that affect the levels and conformational stability of proteins in cells. Maintenance of proper protein homeostasis is essential for cell viability and growth. External stresses and inherent instability of proteins may cause such proteins to misfold and aggregate.... read moreProtein homeostatic processes combat these problems by stabilizing proteins that carry out beneficial functions or by degrading misfolded proteins that are detrimental to the cell. Molecular chaperones and proteases perform a significant subset of these processes.

Molecular chaperones promote protein folding and prevent protein misfolding and aggregation. Molecular chaperones are defined as a group of highly interactive proteins that modulate the folding and unfolding of other proteins, or the assembly and disassembly of protein-protein, protein-DNA, and protein-RNA complexes. In addition, chaperones are known to be involved in many cellular processes and pathways such as protein translocation across membranes, ribosomal RNA processing, and endoplasmic reticulum associated protein degradation (ERAD).

The main proteolytic system involved in protein homeostasis in eukaryotic cells is the proteasome system. The proteasome is a large protein complex that typically recognizes and degrades ubiquitinated substrates. The ubiquitination of substrates is a highly regulated process that is carried out by a large number of ubiquitin ligases. The overall ubiquitin-proteasome system plays critical roles in many cellular pathways including cell cycle, antigen presentation, regulation of gene expression, and many others.

Studies on molecular chaperones and the ubiquitin-proteasome system have typically focused on the detailed biochemical and biophysical analysis of a single or a group of closely related proteins or pathways. However, more recently, several efforts have been made at elucidating a system’s view of protein homeostasis as modulated by molecular chaperones and the ubiquitin-proteasome machinery. This series of talks aims at providing a comprehensive overview on protein homeostasis and the important role it plays in cell stress responses and human diseases.