Control of proteolysis: hormones, nutrients, and the changing role of the proteasome.
OBJECTIVE
The maintenance of protein balance is essential for the proper functioning of a cell. Protein degradation must be controlled to account for the availability of nutrients and hormone signals from the body as a whole. The proteasome is the major cytosolic protein degrading machinery, and is responsible for a considerable proportion of cellular protein degradation. It is thus a prime site for the integration of these various signals. We will examine some recent data regarding the mechanisms for control of the peptidolytic activities of the proteasome, and possible implications for signal transduction and integration.


RESULTS
Nutrients, such as amino acids and fatty acids, have been shown to have effects on proteasome-mediated protein degradation. The ubiquitinylating process is important for the control of protein degradation by the 26S proteasome. Amino acids and hormones control the expression of the necessary components, and can control protein degradation on a relatively longer-term basis. The 20S proteasome has been shown to be capable of degrading proteins without activating subunits. Furthermore, the 20S proteasome is allosterically affected by a number of smaller peptides, suggesting a more immediate mechanism for control. Amino acids and fatty acids have been shown to exert such control in vitro.


CONCLUSIONS
As more is learned about the functioning of the proteasome, the greater appreciation we have of its vital role in the control of cellular metabolism. Recent evidence shows that the proteasome is central to the integration of various nutrient and hormonal signals that the cell receives that may impact on protein metabolism.
Hamel
Frederick G
FG
Research Service, Department of Veterans Affairs Medical Center, and Department of Internal Medicine, University of Nebraska Medical Center, Omaha, 68105, USA. frederick.hamel@med.va.gov
Fawcett
Janet
J
Bennett
Robert G
RG
Duckworth
William C
WC
D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000502:physiology*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
D000596:Amino Acids; D005227:Fatty Acids; D009097:Multienzyme Complexes; D011506:Proteins; D025801:Ubiquitin; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease