Turnover of cellular proteins

Research in the laboratory of A.C. is supported by grants from Prostate Cancer Foundation Israel - Centers of Excellence Program, the Israel Science Foundation - Centers of Excellence Program, a Professorship funded by the Israel Cancer Research fund (ICRE) and the foundation for Promotion of Research in the Technion administered by the Vice President of the Technion for Research. Infrastructural equipment was purchased with the support of the Wolfson Charitable Fund Center of Excellence for studies on Turnover of Cellular Proteins and its Implications to Human Diseases. 

The role of ubiquitin and proteasomes is not limited to the regulation of cyclin as we shall see in Chapter 27, both also take part in the turnover of cellular proteins, a process fundamental to cellular housekeeping. 

The turnover of cellular proteins is a regulated process requiring complex enzyme systems. Proteins to be degraded are conjugated with ubi-quitin, a small conserved protein, in a reaction driven by ATP hydrolysis. The ubiquitin conjugating system is composed of three distinct enzymes. A large, barrel-shaped complex called the proteasome digests the... 

Proteasome, prosome, multimeric protease complex degrading preferentially ubiquitination-targeted intracellular proteins. The name proteasome was proposed to indicate its proteolytic and particulate nature. The ubiquitin-proteasome pathway is important for the regulated degradation of various proteins, since proteolysis and turnover of cellular proteins are essential processes in living cells. From 1989 on it became evident that the proteasome acts as the proteolytic core of a larger ATP-dependent complex. The 26S proteasome complex (Mr 1700 kDa) is the key catalytic protease, and is composed of... 

In the normal turnover of cellular proteins, holo-carboxylases are degraded to biocytin or biotin linked to an oligopeptide containing at most a few amino acid residues (Figure 1). Biotinidase releases biotin for recycling. Genetic deficiencies of holocarboxylase synthetase and biotinidase cause the two types of multiple carboxylase deficiency that were previously designated the neonatal and juvenile forms. 

To date, no mammalian factors specifically involved in ER protein degradation have been isolated. There exist entries in the sequence databases, which share similarity to the yeast Hrdl/Der3, Hrd3 and Deri proteins, respectively, however, the function of these proteins has not been determined so for. Therefore, it remains an open question whether ER protein degradation in mammalian cells requires the activity of similar cellular components that have been shown to mediate turnover of ER proteins in yeast. 

During the normal synthesis and degradation of cellular proteins (protein turnover Chapter 27), some amino acids that are released from protein breakdown and are not needed for new protein synthesis undergo oxidative degradation. 

The Ca2+-dependent neutral proteases called calpains are found within the cells of higher animals. The 705-residue multidomain peptide chain of a chicken calpain contains a papain-like domain as well as a calmodulin-like domain.328 It presumably arose from fusion of the genes of these proteins. At least six calpains with similar properties are known.329 Some have a preference for myofibrillar proteins or neurofilaments.330 They presumably function in normal turnover of these proteins and may play a role in numerous calcium-activated cellular processes.331-3323... 

Blood neutrophils express Mcl-l protein, which is sufficient to ensure the survival of these cells by counteracting the effects of pro-apoptotic proteins. In the absence of continuous expression of this protein (via transcription and translation), the natural turnover of this protein and short half-life will result in a rapid decrease in its cellular levels. When these levels fall below a critical threshold, its protective effects are lost. The activity of the pro-apoptotic proteins then... 

Since turnover can be regarded as involved in the homeostasis of cellular protein level, it may be of interest to consider a case that could... 

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