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Regulation of Protein Metabolism in Muscle

Leonard S. Jefferson, Thomas C. Vary, Scot R. Kimball

10.1002/cphy.cp070216

Source: Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism

Originally published: 2001

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Efficiency of Protein Synthesis: Translational Control
1.1 Role of Insulin in the Regulation of Translation Initiation
1.2 Interactive Roles of Insulin and Amino Acids in the Regulation of Translation Initiation
1.3 Interactive Roles of Insulin and Other Hormones in the Regulation of Protein Synthesis in Skeletal Muscle
2 Capacity for Protein Synthesis: Ribosomal Biogenesis
2.1 Role of Insulin in the Regulation of rRNA Gene Transcription
2.2 Role of Insulin in the Regulation of Synthesis of Ribosomal Proteins
3 Protein Degradation
3.1 The Lyosomal System
3.2 Calcium Activated Proteinases
3.3 The Ubiquitin‐Proteasome System
4 Future Perspectives
Figure 1. Figure 1.

Initiation of protein synthesis. The diagram highlights the two key regulatory steps in translation initiation: the binding of initiator methionyl‐tRNA (met‐tRNA1) to the 40 S ribosomal subunit, mediated by eukaryotic initiation factor 2 (eIF2) and the binding of mRNA to the 43 S preinitiation complex, mediated by eIF4E. In addition, the sequestration of eIF4E into an inactive complex with eIF4E‐binding protein 1 (4E‐BP1) is depicted.
Figure 2. Figure 2.

Potential signal‐transduction pathways in the regulation of translation initiation and rDNA transcription. The protein kinase signal‐transduction pathways activated in response to insulin and/or amino acids and the effect of activation on regulation of general or specific mRNA translation as well as RNA polymerase I are depicted. Whereas amino acids activate the mammalian target of rapamycin (mTOR), and thus stimulate RNA polymerase I and specific mRNA translation, they inhibit Gcn2p, resulting in a decrease in eukaryotic initiation factor 2α (eIF2α) phosphorylation and stimulation of general protein synthesis. PI, phosphatidylinositol; PKB, protein kinase B; GSK‐3, glycogen synthase kinase‐3; 4E‐BP1, eIF4E‐binding protein; Gcn2p, nutrient‐regulated eIF2α kinase.
Figure 3. Figure 3.

Regulatory elements involved in modulation of rDNA transcription. The diagram highlights the key regulatory elements in the control of rDNA transcription by insulin and/or amino acids. Details are provided in the text. UBF, upstream binding factor; SL1, selectivity factor 1.
Figure 4. Figure 4.

Schematic diagram of ubiquitin‐dependent proteolytic pathway. Refer to text for detailed explanation of the different steps involved in the degradation of proteins by this pathway. Ub, ubiquitin; El, ubiquitin‐activating enzyme El; E2, ubiquitin‐conjugating enzyme E2; E3; ubiquitin protein ligase E3.


Figure 1.

Initiation of protein synthesis. The diagram highlights the two key regulatory steps in translation initiation: the binding of initiator methionyl‐tRNA (met‐tRNA1) to the 40 S ribosomal subunit, mediated by eukaryotic initiation factor 2 (eIF2) and the binding of mRNA to the 43 S preinitiation complex, mediated by eIF4E. In addition, the sequestration of eIF4E into an inactive complex with eIF4E‐binding protein 1 (4E‐BP1) is depicted.



Figure 2.

Potential signal‐transduction pathways in the regulation of translation initiation and rDNA transcription. The protein kinase signal‐transduction pathways activated in response to insulin and/or amino acids and the effect of activation on regulation of general or specific mRNA translation as well as RNA polymerase I are depicted. Whereas amino acids activate the mammalian target of rapamycin (mTOR), and thus stimulate RNA polymerase I and specific mRNA translation, they inhibit Gcn2p, resulting in a decrease in eukaryotic initiation factor 2α (eIF2α) phosphorylation and stimulation of general protein synthesis. PI, phosphatidylinositol; PKB, protein kinase B; GSK‐3, glycogen synthase kinase‐3; 4E‐BP1, eIF4E‐binding protein; Gcn2p, nutrient‐regulated eIF2α kinase.



Figure 3.

Regulatory elements involved in modulation of rDNA transcription. The diagram highlights the key regulatory elements in the control of rDNA transcription by insulin and/or amino acids. Details are provided in the text. UBF, upstream binding factor; SL1, selectivity factor 1.



Figure 4.

Schematic diagram of ubiquitin‐dependent proteolytic pathway. Refer to text for detailed explanation of the different steps involved in the degradation of proteins by this pathway. Ub, ubiquitin; El, ubiquitin‐activating enzyme El; E2, ubiquitin‐conjugating enzyme E2; E3; ubiquitin protein ligase E3.

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Article Title: Regulation of Protein Metabolism in Muscle
 

How to Cite

Leonard S. Jefferson, Thomas C. Vary, Scot R. Kimball. Regulation of Protein Metabolism in Muscle. Compr Physiol 2011, Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism: 529-552. First published in print 2001. doi: 10.1002/cphy.cp070216