A. Rocca et al., Involvement of the ubiquitin/proteasome system in sorting of the interleukin 2 receptor beta chain to late endocytic compartments, MOL BIOL CE, 12(5), 2001, pp. 1293-1301
Down-regulation of cell surface growth factor receptors plays a key role in
the tight control of cellular responses. Recent reports suggest that the u
biquitin system, in addition to participating in degradation by the proteas
ome of cytosolic and nuclear proteins, might also be involved in the down-r
egulation of various membrane receptors. We have previously characterized a
signal in the cytosolic part of the interleukin 2 receptor beta chain (IL2
R beta) responsible for its targeting to late endosomes/lysosomes. In this
report, the role of the ubiquitin/proteasome system on the intracellular fa
te of IL2R beta was investigated. Inactivation of the cellular ubiquitinati
on machinery in ts20 cells, which express a thermolabile ubiquitin-activati
ng enzyme E1, leads to a significant decrease in the degradation rate of IL
2R beta, with little effect on its internalization. In addition, we show th
at a fraction of IL2R beta can be monoubiquitinated. Furthermore, mutation
of the lysine residues of the cytosolic region of a chimeric receptor carry
ing the IL2R beta targeting signal resulted in a decreased degradation rate
. When cells expressing IL2R beta were treated either by proteasome or lyso
some inhibitors, a significant decrease in receptor degradation was observe
d. Our data show that ubiquitination is required for the sorting of IL2R be
ta toward degradation. They also indicate that impairment of proteasome fun
ction might more generally affect intracellular routing.