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The second step at which ubiquitination or proteasome action may be implicated is after internalization, in routing of the receptor from early endocytic to late degradation compartments.

The Ubiquitin Proteasome Pathway (UPP) | Boston Biochem

Interestingly, ubiquitination of proteins can be regulated by specific ubiquitin proteases Wilkinson, In this respect, it is worth noting that one of these deubiquitinating enzymes named DUB-2 is induced by IL2 and down-regulated after the initiation of T-cell activation Zhu et al. However, we observed that, in the presence of the proteasome inhibitor, the extent of colocalization of two markers of normally distinct compartments, TfR and Lamp-1, was increased.

Effect of proteasome malfunction in the overall defect of vacuolar integrity was also one of the models proposed for the proteasome-dependent degradation of the a-factor transporter in yeast Loayza and Michaelis, Interestingly, a link between ubiquitin system and maintenance of intracellular integrity has also previously been described Lenk et al. In this report, it was shown, using ts20 mutant cell line, that a functional ubiquitination machinery is necessary for the maturation of autophagic vacuoles.

The role of proteasome in the routing of membrane proteins from the endocytic to degradation compartments is unclear.

Deshaies (Amgen) 3: Targeting the ubiquitin-proteasome system in cancer

One possible mechanism is that proteasome function might be involved in the regulation of a protein playing a crucial role in trafficking through the endocytic pathway. One potential candidate might be the recently described sorting nexin SNX15 Barr et al. Proteasomal degradation of some mammalian receptors has previously been described. For the platelet-derived growth factor Mori et al. We are grateful to Raymond Hellio and Pascal Roux for help with confocal microscopy, Annick Dujeancourt for skillfull technical assistance. The confocal microscope was purchased with a donation from Marcel and Liliane Pollack.

This work was supported by the Association pour la Recherche sur le Cancer no.

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N -acetyl- l - l -leucyl-norleucinal. Molecular Biology of the Cell Vol. Anna Rocca Search for more papers by this author. E-mail address: E-mail Address: adautry pasteur. Add to favorites Download Citations Track Citations. Abstract Down-regulation of cell surface growth factor receptors plays a key role in the tight control of cellular responses.

Overexpression of a novel sorting nexin, SNX15, affects endosome morphology and protein trafficking. Traffic 1 , Structural design and molecular evolution of a cytokine receptor superfamily.

The Role of Proteasome in Apoptosis

USA 87 , Ubiquitin and the control of protein fate in the secretory and endocytic pathways. Cell Dev. The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J. A 26 S protease subunit that binds ubiquitin conjugates.

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Down regulation of high affinity interleukin 2 receptors in a human tumor T cell line: IL2 increases the rate of surface receptor decay. Receptor mediated endocytosis of interleukin 2 in a human tumor T cell line: degradation of interleukin 2 and evidence for the absence of recycling of interleukin 2 receptors. Autocrine growth stimulation of a human T-cell lymphoma line by IL2. USA 82 , Ubiquitin Lys63 is involved in ubiquitination of a yeast plasma membrane protein.

Identification of a novel ubiquitin conjugation motif, required for ligand-induced internalization of the growth hormone receptor. Cell Biol. The ubiquitin system. Gettin'down with ubiquitin: turning off cell-surface receptors, transporters and channels. Trends Cell Biol. Degradation of the met tyrosine kinase receptor by the ubiquitin-proteasome pathway.

A Chinese hamster cell cycle mutant arrested at G2 phase has a temperature-sensitive ubiquitin-activating enzyme, E1. The Gap junction protein connexin43 is degraded via the ubiquitin proteasome pathway. Proteasome inhibitors: valuable new tools for cell biologists. Ubiquitin-activating enzyme, E1, is associated with maturation of autophagic vacuoles. Role for the ubiquitin-proteasome system in the vacuolar degradation of Ste6p, the a -factor transporter in Saccharomyces cerevisiae. Monoubiquitination is sufficient to signal internalization of the maltose transporter in Saccharomyces cerevisiae.

The IL2 receptor complex: its structure, function, and target genes. A di-leucine signal in the ubiquitin moiety.

Ubiquitination of the PEST-like endocytosis signal of the yeast a-factor. Monoubiquitin carries a novel internalization signal that is appended to activated receptors. Regulation of stability and function of the epithelial Na-channel ENaC by ubiquitination. The ubiquitin-proteasome system and endocytosis. Cell Sci. The ubiquitin conjugation system is required for ligand-induced endocytosis and degradation of the growth hormone receptor. Rapid endocytosis of interleukin 2 receptors when clathrin-coated pit endocytosis is inhibited.

A function for monoubiquitination in the internalization of a G protein-coupled receptor. Cell 1 , Interleukin 2 high-affinity receptors expression requires two distinct binding proteins.

Recognition of the polyubiquitin proteolytic signal. Endocytosis and degradation of the growth hormone receptor are proteasome-dependent. USA 90 , Regulating protein degradation by ubiquitination. Today 18 , Only high affinity receptors for interleukin 2 mediate internalization of ligand. USA 83 , The endocytic rate constant. A cellular parameter for quantitating receptor-mediated endocytosis. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating enzymes.

Ozols , Amit Choudhury , Richard E. Pagano , and John R. Dean E. Submitted: 12 December Close Figure Viewer.


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Issue 3, Previous Article Next Article. From the journal: MedChemComm. Identification of an inhibitor of the ubiquitin—proteasome system that induces accumulation of polyubiquitinated proteins in the absence of blocking of proteasome function. This article is part of the themed collection: Chemical Biology for Target Identification and Validation. This article is Open Access. Please wait while we load your content Something went wrong. Try again?

Ubiquitin/Proteasome System

Cited by. Back to tab navigation Download options Please wait Article type: Concise Article. DOI: Author version available: Download author version PDF. Download Citation: Med. Identification of an inhibitor of the ubiquitin—proteasome system that induces accumulation of polyubiquitinated proteins in the absence of blocking of proteasome function C.

Haglund, C. Mohanty, M.