#Stop production synonym series#

We distinguish between population-based bulk biochemical approaches and fluorescence-based single cell methods, which both have their specific advantages and disadvantages ( Table 1). In this review we start by describing the most commonly used methods to monitor protein synthesis and degradation. How cells control the rates of protein synthesis and degradation throughout the cell cycle to allow protein level doubling is not understood. The cell cycle poses several major challenges to gene expression and thus global protein turnover, such as DNA duplication during S phase and chromosome condensation during M phase. In addition, the cell cycle contains several checkpoints, which ensure that the cell is fully prepared to enter the next phase. The transition from one cell cycle phase to the next is regulated by complex molecular programs whose main executors are specific pairs of cyclins and cyclin-dependent kinases (CDKs).

#Stop production synonym series#

Importantly, cycling cells need to be able to precisely double their global protein levels at each cell cycle, as imbalances in protein homeostasis might broadly compromise cellular functions.Ĭycling mammalian cells transit through four consecutive phases: G1, S, G2 and M, each of which consists of a specific series of events that lead to the doubling of protein content to generate two new cells. In contrast, cycling cells such as embryonic stem cells, intestinal stem cells, transit amplifying cells and hematopoietic stem cells continuously need to increase their biomass, thus more proteins need to be synthesized than degraded. In non-dividing (G 0) cells, the levels of the vast majority of proteins are kept constant, even though proteins are still continuously turned over. How this is achieved is not fully understood. Įach individual step involved in protein synthesis and degradation needs to be tightly regulated to control protein expression levels. Polyubiquitinated proteins are then recognized and degraded by the proteasome, a large multisubunit protease complex consisting of two major subcomplexes: the core particle (CP), also referred to as the 20S subunit, which executes the degradation reaction, and the regulatory particle (RP), also referred to as the 19S subunit, which mediates target recognition. E3 enzymes mediate substrate specificity and are consequently the most heterogeneous class of enzymes in the ubiquitination pathway. Polyubiquitination is a multistep process, mediated by 3 main classes of enzymes: ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2) and ubiquitin ligases (E3).

To target a protein for degradation, a chain of ubiquitin molecules is added to the side chain of one of its lysine residues. The major route for selective protein degradation is the ubiquitin-proteasome pathway. In addition, protein lifetimes in fast-cycling cell types, such as prokaryotes or yeast, are usually shorter than in cell types with a longer cell cycle.

In contrast, housekeeping proteins are not subject to short-term fluctuations in their levels and are thus generally long-lived. Regulatory proteins such as transcription factors are often short-lived, which allows for rapid adjustment of their levels in response to internal or external stimuli. Protein degradation generally follows first order decay kinetics, with half-lives varying widely across different proteins depending on their function and the cell type/organism in which they are expressed. Importantly, while often used as a synonym for protein translation, in this review we will employ “protein synthesis” as the net result of all gene expression steps leading to the synthesis of a protein, including transcription, pre-mRNA maturation, mRNA export, and translation.

Newly synthesized proteins can also be subject to a myriad of posttranslational modifications, such as phosphorylation, glycosylation, ubiquitination and many others. It is initiated by the onset of transcription, followed by pre-mRNA maturation, nuclear export of the mRNA, translation and protein folding. The birth of a new protein is the end-result of several consecutive steps and can be regulated at various levels. The precise execution of each step involved in the regulation of protein levels is crucial to the function of the cell and thus to the health of the whole organism, as their mis-regulation can lead to a variety of diseases.

The complex interplay of protein synthesis, folding, trafficking and degradation is referred to as protein homeostasis (or proteostasis). Their continuous synthesis and degradation allow to replace old proteins with new ones and to alter the composition of the proteome during cell differentiation or in response to intra- or extracellular cues. More than 50% of cellular dry weight consists of proteins, which act as building blocks as well as main executors of most cellular functions.