Ubiquitinylation Is Not an Absolute Requirement for Degradation of c-Jun Protein by the 26 S Proteasome

Jariel-Encontre, Isabelle; Pariat, Magali; Martin, François; Carillo, Serge; Salvat, Catherine; Piechaczyk, Marc

doi:10.1074/jbc.270.19.11623

Cited by 146 publications

(83 citation statements)

References 35 publications

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“…Covalent conjugation to the polypeptide ubiquitin seems to be an obligatory step in the degradation of most nuclear and cytosolic short-lived proteins (Ciechanover et al, 1991;Hershko and Ciechanover, 1992;Jentsch, 1992), although in a few cases tagging by ubiquitin is not an absolute requirement for degradation by the proteasome in vitro Rosenberg-Hasson et al, 1989;Jariel-Encontre et al, 1995). The involvement of an ATP-dependent degradation pathway in vitro in the turnover of N-myc and other nuclear regulatory proteins (c-Myc, c-Fos, E1A and p53) has been demonstrated, however high molecular weight ubiquitin conjugates of N-myc were not observed (Ciechanover et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome

et al. 1998

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Section: Introductionmentioning

confidence: 99%

In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome

et al. 1998

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“…For example, degradation of several proteasome substrates including p21/Cip1, c-Jun, c-Fos, p53, and RPN4, are mediated by both ubiquitin-dependent and ubiquitin-independent routes [81][82][83]. Although these proteins are usually ubiquitinated, they are degraded even when their ubiquitination is inhibited.…”

Section: Additional Layers Of Substrate Targetingmentioning

confidence: 99%

Protein targeting to ATP-dependent proteases

Inobe

Matouschek

2008

Current Opinion in Structural Biology

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ATP-dependent proteases control diverse cellular processes by degrading specific regulatory proteins. Understanding how these regulatory proteins are targeted to ATP-dependent proteases is of central importance to understanding their biological role as regulators. Recent work has shown that protein substrates are specifically transferred to ATP-dependent proteases through different routes. These routes can function in parallel or independently. In all of these targeting mechanisms it can be useful to separate two steps: substrate binding to the protease and initiation of degradation.To be active, newly synthesized protein chains must fold into three-dimensional structures, but regulated unfolding is also critically important in some biological processes, such as protein degradation by ATP-dependent proteases and protein translocation across membranes [1]. Unfolding is required during degradation because the proteolytic sites of the ATP-dependent proteases are sequestered deep inside the proteases' structures and accessible only through narrow openings. Similarly, unfolding is required during several translocation processes because the protein import channels in some organelles are not wide enough for native proteins to fit through them. The mechanisms of unfolding in both types of processes are similar to each other but different from that of unfolding induced by heat or chemical denaturants. Here we discuss how the requirement for protein unfolding during degradation affects the way ATPdependent proteases select their substrates. ATP-dependent proteasesATP-dependent proteases degrade short-lived regulatory proteins and thereby control cellular processes such as signal transduction, cell cycle, and gene transcription. The proteases also clear misfolded and aggregated proteins from the cell and produce some of the peptides to be displayed at cell surface as part of adaptive immune response. In eukaryotes, these functions are performed mainly by the proteasome. In prokaryotes and the organelles of eukaryotes, the functions are fulfill by analogues of the proteasome, such as the ClpAP, ClpXP, HslUV, FtsH, and Lon proteases. Although ATP-dependent proteases show only relatively little sequence identity, they share a common architecture [2].The ATP-dependent proteases all form large multisubunit particles (Figure 1). In the simplest case, FtsH protease, the particle consists 6 copies of a 71 kDa subunit forming a complex of approximately 425 kDa, and in the most complex case, the proteasome, the particle consists of some 40 different subunits forming a complex of 2 MDa molecular weight [3,4]. The subunits are mostly arranged in six or seven subunit rings that stack on top of each other to

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“…It is assumed that the Ub-protein ligases (E3s) are the recognition elements, or that ubiquitination of abnormal proteins may follow their selective binding to molecular chaperones (22). Although Ub conjugation is essential for the rapid elimination of many regulatory and mutant polypeptides (2,23) and for accelerated proteolysis under certain physiological conditions (24 -26), proteasome-mediated degradation of some proteins can occur without ubiquitination (27)(28)(29). While ubiquitination of proteins generally enhances their breakdown (30,31), in vitro certain unfolded proteins and the short lived enzyme, ornithine decarboxylase, can be hydrolyzed by proteasomes rapidly in an ATP-dependent manner in the absence of ubiquitination (27,32).…”

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confidence: 99%

Ca2+-free Calmodulin and Calmodulin Damaged byin Vitro Aging Are Selectively Degraded by 26 S Proteasomes without Ubiquitination

Tarcsa¹,

Szymańska²,

Lecker³

et al. 2000

Journal of Biological Chemistry

104

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The ubiquitin-proteasome pathway is believed to selectively degrade post-synthetically damaged proteins in eukaryotic cells. To study this process we used calmodulin (CaM) as a substrate because of its importance in cell regulation and because it acquires isoaspartyl residues in its Ca 2؉ -binding regions both in vivo and after in vitro "aging" (incubation for 2 weeks without Ca 2؉ ). When microinjected into Xenopus oocytes, in vitro aged CaM was degraded much faster than native CaM by a proteasome-dependent process. Similarly, in HeLa cell extracts aged CaM was degraded at a higher rate, even though it was not conjugated to ubiquitin more rapidly than the native species. Ca 2؉ stimulated the ubiquitination of both species, but inhibited their degradation. Thus, for CaM, ubiquitination and proteolysis appear to be dissociated. Accordingly, purified muscle 26 S proteasomes could degrade aged CaM and native Ca 2؉ -free (apo) CaM without ubiquitination. Addition of Ca 2؉ dramatically reduced degradation of the native molecules but only slightly reduced the breakdown of the aged species. Thus, upon Ca 2؉ binding, native CaM assumes a non-degradable conformation, which most of the agedamaged species cannot assume. Thus, flexible conformations, as may arise from age-induced damage or the absence of ligands, can promote degradation directly by the proteasome without ubiquitination.

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Ubiquitinylation Is Not an Absolute Requirement for Degradation of c-Jun Protein by the 26 S Proteasome

Cited by 146 publications

References 35 publications

In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome

In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome

Protein targeting to ATP-dependent proteases

Ca2+-free Calmodulin and Calmodulin Damaged byin Vitro Aging Are Selectively Degraded by 26 S Proteasomes without Ubiquitination

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