Regulation of the Polycomb protein RING1B ubiquitination by USP7

Bie, Prim de; Zaaroor-Regev, Daphna; Ciechanover, Aaron

doi:10.1016/j.bbrc.2010.08.082

Cited by 63 publications

(72 citation statements)

References 24 publications

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“…1A and B), in agreement with data from a previous report (26). None of these interactions were disrupted upon benzonase treatment of the nuclear extracts, indicating that neither DNA nor RNA is bridging these interactions (Fig.…”

Section: Usp7 Interacts With Prc14 and Scml2supporting

confidence: 92%

“…In contrast, Maertens et al (25) also recovered small amounts of USP7 by purification of MEL18. Also, direct binding of USP7 to the RING finger domains of RING1B, BMI1, and MEL18 has been detected in vitro (25,26). However, the integrity of PRC1.4 and PRC1.2 involves the heterodimerization of the RING domains of RING1B and BMI1 or MEL18, which are then bound by the E2 ubiquitin-conjugating enzyme UbcH5c (27,28).…”

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confidence: 99%

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USP7 Cooperates with SCML2 To Regulate the Activity of PRC1

Lecona

Narendra

Reinberg

2015

Molecular and Cellular Biology

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USP7 is a protein deubiquitinase with an essential role in development. Here, we provide evidence that USP7 regulates the activity of Polycomb repressive complex 1 (PRC1) in coordination with SCML2. There are six versions of PRC1 defined by the association of one of the PCGF homologues (PCGF1 to PCGF6) with the common catalytic subunit RING1B. First, we show that SCML2, a Polycomb group protein that associates with PRC1.2 (containing PCGF2/MEL18) and PRC1.4 (containing PCGF4/ BMI1), modulates the localization of USP7 and bridges USP7 with PRC1.4, allowing for the stabilization of BMI1. Chromatin immunoprecipitation (ChIP) experiments demonstrate that USP7 is found at SCML2 and BMI1 target genes. Second, inhibition of USP7 leads to a reduction in the level of ubiquitinated histone H2A (H2Aub), the catalytic product of PRC1 and key for its repressive activity. USP7 regulates the posttranslational status of RING1B and BMI1, a specific component of PRC1.4. Thus, not only does USP7 stabilize PRC1 components, its catalytic activity is also necessary to maintain a functional PRC1, thereby ensuring appropriate levels of repressive H2Aub.

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Section: Usp7 Interacts With Prc14 and Scml2supporting

confidence: 92%

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confidence: 99%

USP7 Cooperates with SCML2 To Regulate the Activity of PRC1

Lecona

Narendra

Reinberg

2015

Molecular and Cellular Biology

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“…74 Other E3 ligases were shown to be targeted by USP7 including ICP0, MARCH7, and RING1B. [74][75][76] USP7 removes both self-and E6-AP-generated ubiquitin chains from RING1B, thereby regulating its stability (Figure 3). 75 Therefore, it is not surprising that USP7 was also shown to exert a regulatory effect on the expression of polycomb target genes.…”

Section: Regulation Of E3s By Deubiquitinationmentioning

confidence: 99%

“…[74][75][76] USP7 removes both self-and E6-AP-generated ubiquitin chains from RING1B, thereby regulating its stability (Figure 3). 75 Therefore, it is not surprising that USP7 was also shown to exert a regulatory effect on the expression of polycomb target genes. 77 Activation of the NF-kB pathway trough ligand-induced oligomerization and self-ubiquitination of TRAF6 is regulated through the actions of ubiquitin linkage-specific DUBs.…”

Section: Regulation Of E3s By Deubiquitinationmentioning

confidence: 99%

Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms

2011

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Ubiquitin modification of many cellular proteins targets them for proteasomal degradation, but in addition can also serve non-proteolytic functions. Over the last years, a significant progress has been made in our understanding of how modification of the substrates of the ubiquitin system is regulated. However, little is known on how the ubiquitin system that is comprised of B1500 components is regulated. Here, we discuss how the biggest subfamily within the system, that of the E3 ubiquitin ligases that endow the system with its high specificity towards the numerous substrates, is regulated and in particular via self-regulation mediated by ubiquitin modification. Ligases can be targeted for degradation in a self-catalyzed manner, or through modification mediated by an external ligase(s). In addition, non-proteolytic functions of self-ubiquitination, for example activation of the ligase, of E3s are discussed. Cell Death and Differentiation (2011) 18, 1393-1402 doi:10.1038/cdd.2011; published online 4 March 2011One of the major roles of the covalent modification of cellular proteins by ubiquitin is signaling them for proteasomal degradation ( Figure 1). The first step of the modification is catalyzed by the ubiquitin-activating enzyme, E1, which generates a high-energy thiol ester intermediate that is subsequently transferred to the second enzyme, a ubiquitinconjugating enzyme, E2. The third step ascertains substrate specificity, and is catalyzed by one of the numerous (B650) ubiquitin ligases, E3s. Typically, it results in the formation of an isopeptide bond between the C-terminal Gly of ubiquitin and an e-NH 2 group of an internal Lys of the substrate. Less frequently, it can generate a linear peptide bond with the a-NH 2 group, a thiol ester bond with an internal Cys, or an ester bond with a Thr or Ser. The three-step cascade of reactions is repeated, where additional ubiquitin moieties are attached sequentially to one another in an isopeptide bond involving one of the seven internal Lys residues in the ubiquitin moiety, thus generating a polyubiquitin chain. Lys48-based chains serve as a signal for proteasomal degradation, whereas chains based on other internal Lys residues, or modification by single moiety(ies) can serve non-proteolytic functions.Ligases fall into two main families: RING (really interesting new gene) and HECT (homologous to the E6-AP carboxy terminus) domain-containing E3s. RING ligases serve as scaffolds that facilitate direct transfer of ubiquitin from the E2 to the target protein. HECT E3s contain an active Cys residue to which ubiquitin binds prior to its transfer to the substrate (Figure 1). There are B600 RING finger and B30 HECT ligases in humans. Smaller families of ligases (U-box, plant homology domain, and zinc finger) have also been described.An important problem relates to regulation of the ubiquitin system components, and in particular to that of the ligases that are the specific substrate-recognizing elements. 1,2 Phosphorylation of an E3 can activate the protein, such as the ca...

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“…One such E3:DUB pair is MDM2:USP7, with MDM2 being stabilized by USP7-mediated deubiquitination (14). In contrast, Usp7 can act in partnership with the E6-AP RING-ligase to catalyze the removal of Ub conjugates from RING1b, with E6-AP mediating the attachment of Lys 48 -linked Ub conjugates that promote the proteasomal degradation of RING1b (15). Although most characterized DUBs have been reported to function via their Ubprotease activity, in some cases DUBs can inhibit ubiquitination and degradation of substrates independent of their catalytic activity (16 -18).…”

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confidence: 99%

Ataxin-3 Deubiquitination Is Coupled to Parkin Ubiquitination via E2 Ubiquitin-conjugating Enzyme

Durcan

Kontogiannea

Bédard

et al. 2012

Journal of Biological Chemistry

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Background:The deubiquitinating enzyme (DUB) ataxin-3 opposes the E3 ubiquitin-ligase activity of parkin, however, the mechanism involved is unclear. Results: Ataxin-3 opposes parkin ubiquitination by regulating the E2 ubiquitin-conjugating enzyme. Conclusion: The components within a E2⅐E3⅐DUB complex are functionally coupled to fine-tune the overall extent of ubiquitination. Significance: The work broadens our understanding of the intricate interplay between E3s, DUBs, and the ubiquitination machinery.

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Regulation of the Polycomb protein RING1B ubiquitination by USP7

Cited by 63 publications

References 24 publications

USP7 Cooperates with SCML2 To Regulate the Activity of PRC1

USP7 Cooperates with SCML2 To Regulate the Activity of PRC1

Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms

Ataxin-3 Deubiquitination Is Coupled to Parkin Ubiquitination via E2 Ubiquitin-conjugating Enzyme

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