The role of the molecular chaperone CCT in protein folding and mediation of cytoskeleton-associated processes: implications for cancer cell biology

The chaperonin-containing tailless complex polypeptide 1 (CCT) is required in vivo for the folding of newly synthesized tubulin and actin proteins and is thus intrinsically connected to all cellular processes that rely on the microtubule and actin filament components of the cytoskeleton, both of which are highly regulated and dynamic assemblies. In addition to CCT acting as a protein folding oligomer, further modes of CCT action mediated either by the CCT oligomer itself or via CCT subunits in their monomeric forms can influence processes associated with assembled actin filaments and microtubules. Thus, there is an extended functional role for CCT with regard to its major folding substrates with a complex interplay between CCT as folding machine for tubulin/actin and as a modulator of processes involving the assembled cytoskeleton. As cell division, directed cell migration, and invasion are major drivers of cancer development and rely on the microtubule and actin filament components of the cytoskeleton, CCT activity is fundamentally linked to cancer. Furthermore, the CCT oligomer also folds proteins connected to cell cycle progression and interacts with several other proteins that are linked to cancer such as tumor-suppressor proteins and regulators of the cytoskeleton, while CCT monomer function can influence cell migration. Thus, understanding CCT activity is important for many aspects of cancer cell biology and may reveal new ways to target tumor growth and invasion.