Ubiquitin stripping
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《细胞学杂志》
Receptors tagged for destruction can be rescued by enzymes that remove the tag, according to McCullough et al. (page 487). Thus, like kinases, ubiquitin ligases are opposed by activities that undo their work.
Activated internalized receptors are tagged with ubiquitin for sorting to lysosomes from endosomes rather than recycling back to the plasma membrane. Until now, ubiquitin was thought to be removed only just before the receptor's destruction to preserve cellular ubiquitin pools. But the new work shows that an endosomal enzyme called AMSH acts early enough to prevent receptor degradation.
AMSH saves receptors by removing the destruction tags. In vitro, AMSH removed ubiquitin from substrates such as the EGF receptor. In cells, a dominant-negative AMSH mutant caused an accumulation of ubiquitin at endosomes.
More ubiquitination means more destruction. In cells with reduced levels of AMSH, the rate of EGF receptor degradation after stimulation with EGF was twice that of cells with normal AMSH levels.
AMSH is probably not the only endosome-associated deubiquitinating enzyme (DUB). The authors show that another DUB, called UBPY, has cleavage preferences that differ from those of AMSH. UBPY is thought to recycle ubiquitin before degradation, but perhaps it also regulates degradation—either of different substrates or at other steps in the pathway from the surface to lysosomes.(Ubiquitin (blue) builds up on receptors )
Activated internalized receptors are tagged with ubiquitin for sorting to lysosomes from endosomes rather than recycling back to the plasma membrane. Until now, ubiquitin was thought to be removed only just before the receptor's destruction to preserve cellular ubiquitin pools. But the new work shows that an endosomal enzyme called AMSH acts early enough to prevent receptor degradation.
AMSH saves receptors by removing the destruction tags. In vitro, AMSH removed ubiquitin from substrates such as the EGF receptor. In cells, a dominant-negative AMSH mutant caused an accumulation of ubiquitin at endosomes.
More ubiquitination means more destruction. In cells with reduced levels of AMSH, the rate of EGF receptor degradation after stimulation with EGF was twice that of cells with normal AMSH levels.
AMSH is probably not the only endosome-associated deubiquitinating enzyme (DUB). The authors show that another DUB, called UBPY, has cleavage preferences that differ from those of AMSH. UBPY is thought to recycle ubiquitin before degradation, but perhaps it also regulates degradation—either of different substrates or at other steps in the pathway from the surface to lysosomes.(Ubiquitin (blue) builds up on receptors )