In 1942, Schönheimer introduced the concept ‘that all constituents of living matter, whether functional or structural, of simple or of complex constitution, are in a steady state of rapid flux’. This notion was advanced with the discovery of intracellular protein degradation machinery: it is now clear that cellular protein homeostasis is tightly controlled and that degradation of proteins via the lysosome and the ubiquitin-proteasome system is functionally on par with transcriptional and translational control. This enables tight and selective control of the presence and amounts of specific proteins and is important for all aspects of cellular functions, from metabolism to cell division, cell differentiation and regulation of cell-environment interactions.
In order to facilitate research in protein degradation, we developed a fluorescent protein based method, entitled ‘tandem fluorescent protein timers’ (tFTs) that enables direct visualization of protein degradation inside living cells, from yeast to mammals. See for a recent application to visualize cytokine signaling in fish and to detect a new cellular quality control pathway at the inner nuclear membrane.