Proteasome function and protein biosynthesis.
OBJECTIVE
Protein synthesis and degradation govern protein turnover, which underlies the adaptation of organisms to changing developmental, physiological and environmental needs. The cellular mechanisms of these processes have been increasingly uncovered. Recent findings establishing additional links between protein synthesis and degradation are the topic of this review.


RESULTS
Several major developments in the field have taken place recently. First, the role of lysosomal-autophagosomal degradation, the established amino acid supplier for protein synthesis, has been demonstrated for additional diverse aspects of cellular physiology. Second, cytosolic protein degradation initiated by the proteasome has been assigned a critical role in sustaining ongoing protein synthesis upon acute nutrient restriction. A number of regulatory possibilities to modulate the intracellular amino acid flux by means of proteasomal degradation are discussed. Finally, the field of translation factor regulation by their degradation has emerged recently and is described here.


CONCLUSIONS
The elucidation of mechanisms determining protein turnover and, thus, cellular adaptation will help us to understand the (patho)physiological conditions caused or accompanying acute and chronic nutrient deficiencies and should lead to new therapeutic strategies to handle them.
Vabulas
Ramunas M
RM
Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany. vabulas@biochem.mpg.de
D000222:Adaptation, Physiological; D000596:Amino Acids / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
D000596:Amino Acids; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex