Advances in protein turnover analysis at the global level and biological insights

Abstract

The concept of a dynamic state of body constituents, a precursor of the modern term of proteome dynamics, was conceived over a century ago. But, not until recently can we examine the dynamics of individual "constituents" for example, proteins at a truly global level. The path of advancement in our understanding of protein turnover at the global level is marked by the introduction of some key technological innovations. These methods include the isotopic tracer technique in the 1930s, the two-dimensional gel electrophoresis technique in the 1970s, the sector mass spectrometer that could analyze isotopomers of peptides in the early 1990s, the 2D gel/MALDI-TOF proteomics technology in the late 1990s, the booming liquid chromatography/mass spectrometry proteomics technology in this decade, and the recently emerging protein-tagging approaches that offer single-cell resolution for protein turnover measurements. The long-standing inquiry raised in the 1950s about the existence of a dynamic state in different organisms at different physiological conditions can now be answered with an individual "constituent" resolution on a truly global scale. Now it appears that protein degradation is not necessarily an end to the protein function. Rather, it can be the start of a new function because protein degradation clears the way for the action of other proteins. Protein turnover participates in a multi-layer complex regulatory network and shares equal importance with gene transcription and protein translation. The advances in technologies for protein turnover analysis and the improved understanding of the biological role of protein turnover will likely help to solve some long-standing biomedical problems such as the tuberculosis disease that at the present day still affects one-third of the world population.

Measuring the turnover rates of Arabidopsis proteins using deuterium oxide: an auxin signaling case study

“…The kinetics of protein turnover are critical to the cellular regulatory processes that allow plants to rapidly respond to changing environmental conditions, or intracellular signal molecules, by altering the levels of key proteins. These considerations indicate that the determination of protein turnover often has the same or greater importance as gene transcription and protein translation when characterizing functional changes in the cell (Li, 2009). To date, much of the protein analysis in plants has focused on the comparison of protein abundance under different conditions, and the changes in the steadystate levels of proteins is frequently and, often erroneously, cited as a measure of the dynamics of protein metabolism.…”

Mechanisms of protein balance in skeletal muscle

“…Another approach uses biotinylated puromycin to label newly synthesized proteins in cell-free conditions, followed by proteomic analysis to generate a snapshot of the translatome [27,28]. These protein tagging approaches to assess the proteome are faster and easier than two-dimensional gel electrophoresis methods to assess the proteome [10,29]. …”

Quantitation of Human Peptides and Proteins Via MS: Review of Analytically Validated Assays

“…The relative abundance of the tracer (commonly referred to as isotope enrichment) in the protein pool is then measured at multiple time points. With additional information about the precursor iso-tope enrichment and the protein concentration, the kinetics of tracer incorporation and clearance can be modeled to yield a fractional synthetic rate (FSR) and a fractional clearance rate (FCR) that describes protein metabolism [68].…”