The Chaperone code has been identified as one of the main regulatory mechanisms underlying cell function in biology. While the genetic code specifies how DNA makes proteins, while the histone code rules genomic transactions, the chaperone code stipulates how proteins produce a functional proteome.
The chaperone code refers to the combinatorial array of posttranslational modifications - i.e. phosphorylation, acetylation, ubiquitination, methylation, etc - that target molecular chaperones to modulate their activity. Molecular chaperones are proteins specialized in folding and unfolding of the other cellular proteins and assembly and dismantling of protein complexes, thereby orchestrating the dynamic organization of the proteome. As a consequence, a limited number of chaperones must be able to act on a very large number of substrates in a highly regulated manner.
The chaperone code concept posits that combinations of posttranslational modifications at the surface of chaperones, including phosphorylation, acetylation, methylation, ubiquitination, etc, control protein folding/unfolding and protein complex assembly/disassembly by stipulating substrate specificity, activity, subcellular localization and co-factor binding. This conclusion emerges from the analysis of nearly two hundred reports in the literature, including a key article published in 2013 reporting on the discovery of a novel family of methyltransferases that preferentially target and regulate molecular chaperones. Because posttranslational modifications are marks that can be added and removed rapidly, they provide an efficient mechanism to explain the plasticity observed in proteome organization during cell growth and development.
A large number of diseases, including degenerative neuromuscular disorders and cancer, are associated with dysfunction of molecular chaperones. Decrypting and reprogramming the chaperone code represents a gigantic initiative that generates new hopes for the development of therapeutics for degenerative diseases.