UBP41 is a proapoptotic ubiquitin-specific protease.
We have isolated Ubp41, a ubiquitin-specific protease, in a screen for proapoptoticgenes. We found that overexpression of Ubp41 is sufficient to elicit all features of apoptosis in human cells. In contrast, an enzymatically defective UBP41 mutant and homologous ubiquitin-processing protease family members did not significantly induce cell death. Overexpression of Ubp41 resulted in a strong deubiquitination of a broad range of proteins, but surprisingly did not lead to a stabilization of protein substrates known to be regulated by the ubiquitin-proteasome system such as the cell cycle factors p21 and p27. Hence, in contrast to the proteasome inhibitor MG132, Ubp41 overexpression did not arrest cells in G(2)/M. Rather, overexpression of hUbp41 seems to interfere with the ubiquitin-system and to cause the activation of apoptosis pathways by stabilizing specific substrates. Hence, for the first time we found that a member of the deubiquitinating enzymes has a direct proapoptotic activity additionally tightening the connection between apoptosis and the ubiquitin-proteasome system.
Gewies
Andreas
A
Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany.
Grimm
Stefan
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase
D009097:Multienzyme Complexes; D025801:Ubiquitin; D004247:DNA; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex