PURPOSE OF REVIEW: Although the suppression of protein breakdown plays a major 
role in the growth of the adult kidney in conditions that cause renal 
hypertrophy, the pathways responsible for controlling proteolysis and the 
substrates being destroyed have only recently been investigated. This review 
focuses on the role of the ubiquitin-proteasome pathway in regulating specific 
substrates during kidney growth, and the role of the lysosomal pathways in the 
suppression of general protein breakdown and of the substrates of 
chaperone-mediated autophagy.
RECENT FINDINGS: New insights into the regulation of specific ubiquitin ligases 
demonstrate how the cell controls the destruction of particular substrates 
important for growth, including hypoxia-inducible factors and the cell cycle 
inhibitor, p27. In cell culture, growth factors suppress the lysosomal pathway 
of chaperone-mediated autophagy leading to the accumulation of specific 
cytoplasmic proteins containing KFERQ motifs. In a variety of systems, including 
cultured renal tubular cells, phosphoinositol 3 kinase activity and its 
downstream mediators control lysosomal proteolysis.
SUMMARY: Specific ubiquitin ligases and the pathways that control their 
substrate recognition may be key signalling intermediaries for cell growth, but 
global alterations in lysosomal pathways account for the decrease in general 
proteolysis. Functional KFERQ motifs mark proteins that are important in renal 
growth, including enzymes responsible for the characteristic shift to glycolytic 
metabolism during growth, transcription factors, and signalling molecules. As 
altering phosphoinositol 3 kinase changes patterns of vesicular trafficking, it 
is possible that the regulation of intracellular trafficking may underlie the 
changes seen in lysosomal proteolysis with growth.