Hug and hold tight: Dimerization controls the turnover of the ubiquitin-conjugating enzyme UBE2S

2020 ◽  
Vol 13 (654) ◽  
pp. eabd9892
Author(s):  
Anja Bremm
Keyword(s):  
Half Life ◽  
Anaphase Promoting Complex ◽  
Ubiquitin Chain ◽  
Precise Control ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzymes ◽  
Chain Synthesis ◽  
Ubiquitin Conjugating Enzymes ◽  
Conjugating Enzyme

Precise control of the activity and abundance of ubiquitin-conjugating enzymes (E2s) ensures fidelity in ubiquitin chain synthesis. In this issue of Science Signaling, Liess et al. demonstrate that the human anaphase-promoting complex (APC/C)–associated E2 UBE2S adopts an autoinhibited dimeric state that increases the half-life of UBE2S by preventing its autoubiquitination-driven turnover.

scholarly journals OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination

2018 ◽  
Vol 293 (47) ◽  
pp. 18285-18295 ◽  
Author(s):  
Nagesh Pasupala ◽  
Marie E. Morrow ◽  
Lauren T. Que ◽  
Barbara A. Malynn ◽  
Averil Ma ◽  
...  
Keyword(s):  
Polyubiquitin Chains ◽  
Protein Ubiquitination ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzymes ◽  
E2 Enzymes ◽  
Ubiquitin Conjugating Enzymes ◽  
In Cells ◽  
Conjugating Enzyme

OTUB1 is a deubiquitinating enzyme that cleaves Lys-48–linked polyubiquitin chains and also regulates ubiquitin signaling through a unique, noncatalytic mechanism. OTUB1 binds to a subset of E2 ubiquitin-conjugating enzymes and inhibits their activity by trapping the E2∼ubiquitin thioester and preventing ubiquitin transfer. The same set of E2s stimulate the deubiquitinating activity of OTUB1 when the E2 is not charged with ubiquitin. Previous studies have shown that, in cells, OTUB1 binds to E2-conjugating enzymes of the UBE2D (UBCH5) and UBE2E families, as well as to UBE2N (UBC13). Cellular roles have been identified for the interaction of OTUB1 with UBE2N and members of the UBE2D family, but not for interactions with UBE2E E2 enzymes. We report here a novel role for OTUB1–E2 interactions in modulating E2 protein ubiquitination. We observe that Otub1−/− knockout mice exhibit late-stage embryonic lethality. We find that OTUB1 depletion dramatically destabilizes the E2-conjugating enzyme UBE2E1 (UBCH6) in both mouse and human OTUB1 knockout cell lines. Of note, this effect is independent of the catalytic activity of OTUB1, but depends on its ability to bind to UBE2E1. We show that OTUB1 suppresses UBE2E1 autoubiquitination in vitro and in cells, thereby preventing UBE2E1 from being targeted to the proteasome for degradation. Taken together, we provide evidence that OTUB1 rescues UBE2E1 from degradation in vivo.

scholarly journals Two Ubiquitin-Conjugating Enzymes, UbcP1/Ubc4 and UbcP4/Ubc11, Have Distinct Functions for Ubiquitination of Mitotic Cyclin

2003 ◽  
Vol 23 (10) ◽  
pp. 3497-3505 ◽  
Author(s):  
Hiroaki Seino ◽  
Tsutomu Kishi ◽  
Hideo Nishitani ◽  
Fumiaki Yamao
Keyword(s):  
Fission Yeast ◽  
Ubiquitin Proteasome System ◽  
High Expression ◽  
Mitotic Cyclin ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzymes ◽  
Ubiquitin Conjugating Enzymes ◽  
Mutant Cells ◽  
Conjugating Enzyme

ABSTRACT Cell cycle events are regulated by sequential activation and inactivation of Cdk kinases. Mitotic exit is accomplished by the inactivation of mitotic Cdk kinase, which is mainly achieved by degradation of cyclins. The ubiquitin-proteasome system is involved in this process, requiring APC/C (anaphase-promoting complex/cyclosome) as a ubiquitin ligase. In Xenopus and clam oocytes, the ubiquitin-conjugating enzymes that function with APC/C have been identified as two proteins, UBC4 and UBCx/E2-C. Previously we reported that the fission yeast ubiquitin-conjugating enzyme UbcP4/Ubc11, a homologue of UBCx/E2-C, is required for mitotic transition. Here we show that the other fission yeast ubiquitin-conjugating enzyme, UbcP1/Ubc4, which is homologous to UBC4, is also required for mitotic transition in the same manner as UbcP4/Ubc11. Both ubiquitin-conjugating enzymes are essential for cell division and directly required for the degradation of mitotic cyclin Cdc13. They function nonredundantly in the ubiquitination of CDC13 because a defect in ubcP1/ubc4 + cannot be suppressed by high expression of UbcP4/Ubc11 and a defect in ubcP4/ubc11 + cannot be suppressed by high expression of UbcP1/Ubc4. In vivo analysis of the ubiquitinated state of Cdc13 shows that the ubiquitin chains on Cdc13 were short in ubcP1/ubc4 mutant cells while ubiquitinated Cdc13 was totally reduced in ubcP4/ubc11 mutant cells. Taken together, these results indicate that the two ubiquitin-conjugating enzymes play distinct and essential roles in the degradation of mitotic cyclin Cdc13, with the UbcP4/Ubc11-pathway initiating ubiquitination of Cdc13 and the UbcP1/Ubc4-pathway elongating the short ubiquitin chains on Cdc13.

scholarly journals A Giant Ubiquitin-conjugating Enzyme Related to IAP Apoptosis Inhibitors

1998 ◽  
Vol 141 (6) ◽  
pp. 1415-1422 ◽  
Author(s):  
Hans-Peter Hauser ◽  
Michael Bardroff ◽  
George Pyrowolakis ◽  
Stefan Jentsch
Keyword(s):  
Covalent Attachment ◽  
Protein Protein Interaction ◽  
Small Proteins ◽  
The Family ◽  
Golgi Compartment ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzymes ◽  
And Function ◽  
Ubiquitin Conjugating Enzymes ◽  
Conjugating Enzyme

Ubiquitin-conjugating enzymes (UBC) catalyze the covalent attachment of ubiquitin to target proteins and are distinguished by the presence of a UBC domain required for catalysis. Previously identified members of this enzyme family are small proteins and function primarily in selective proteolysis pathways. Here we describe BRUCE (BIR repeat containing ubiquitin-conjugating enzyme), a giant (528-kD) ubiquitin-conjugating enzyme from mice. BRUCE is membrane associated and localizes to the Golgi compartment and the vesicular system. Remarkably, in addition to being an active ubiquitin-conjugating enzyme, BRUCE bears a baculovirus inhibitor of apoptosis repeat (BIR) motif, which to this date has been exclusively found in apoptosis inhibitors of the IAP-related protein family. The BIR motifs of IAP proteins are indispensable for their anti–cell death activity and are thought to function through protein–protein interaction. This suggests that BRUCE may combine properties of IAP-like proteins and ubiquitin-conjugating enzymes and indicates that the family of IAP-like proteins is structurally and functionally more diverse than previously expected.

scholarly journals The Tail of a Ubiquitin-conjugating Enzyme Redirects Multi-ubiquitin Chain Synthesis from the Lysine 48-linked Configuration to a Novel Nonlysine-linked Form

1996 ◽  
Vol 271 (46) ◽  
pp. 28766-28771 ◽  
Author(s):  
Robert Hodgins ◽  
Chantelle Gwozd ◽  
Terra Arnason ◽  
Maxwell Cummings ◽  
Michael J. Ellison
Keyword(s):  
Ubiquitin Chain ◽  
Ubiquitin Conjugating Enzyme ◽  
Chain Synthesis ◽  
Conjugating Enzyme

scholarly journals Cell Cycle-Dependent Expression of Mammalian E2-C Regulated by the Anaphase-Promoting Complex/Cyclosome

2000 ◽  
Vol 11 (8) ◽  
pp. 2821-2831 ◽  
Author(s):  
Atsushi Yamanaka ◽  
Shigetsugu Hatakeyama ◽  
Kin-ichiro Kominami ◽  
Masatoshi Kitagawa ◽  
Masaki Matsumoto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Substrate Specificity ◽  
Critical Role ◽  
Anaphase Promoting Complex ◽  
Polyubiquitin Chain ◽  
M Phase ◽  
Ubiquitin Conjugating Enzyme ◽  
Recognition Motifs ◽  
Cycle Dependent ◽  
Conjugating Enzyme

Progression through mitosis requires the precisely timed ubiquitin-dependent degradation of specific substrates. E2-C is a ubiquitin-conjugating enzyme that plays a critical role with anaphase-promoting complex/cyclosome (APC/C) in progression of and exit from M phase. Here we report that mammalian E2-C is expressed in late G2/M phase and is degraded as cells exit from M phase. The mammalian E2-C shows an autoubiquitinating activity leading to covalent conjugation to itself with several ubiquitins. The ubiquitination of E2-C is strongly enhanced by APC/C, resulting in the formation of a polyubiquitin chain. The polyubiquitination of mammalian E2-C occurs only when cells exit from M phase. Furthermore, mammalian E2-C contains two putative destruction boxes that are believed to act as recognition motifs for APC/C. The mutation of this motif reduced the polyubiquitination of mammalian E2-C, resulting in its stabilization. These results suggest that mammalian E2-C is itself a substrate of the APC/C-dependent proteolysis machinery, and that the periodic expression of mammalian E2-C may be a novel autoregulatory system for the control of the APC/C activity and its substrate specificity.

scholarly journals The Fission Yeast Ubiquitin-Conjugating Enzymes UbcP3, Ubc15, and Rhp6 Affect Transcriptional Silencing of the Mating-Type Region

2002 ◽  
Vol 1 (4) ◽  
pp. 613-625 ◽  
Author(s):  
Inga Sig Nielsen ◽  
Olaf Nielsen ◽  
Johanne M. Murray ◽  
Geneviève Thon
Keyword(s):  
Fission Yeast ◽  
Rna Polymerase Ii ◽  
Mating Type ◽  
26S Proteasome ◽  
Obvious Effect ◽  
Type Region ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzymes ◽  
Ubiquitin Conjugating Enzymes ◽  
Active Site Mutants

ABSTRACT Genes transcribed by RNA polymerase II are silenced when introduced near the mat2 or mat3 mating-type loci of the fission yeast Schizosaccharomyces pombe. Silencing is mediated by a number of gene products and cis-acting elements. We report here the finding of novel trans-acting factors identified in a screen for high-copy-number disruptors of silencing. Expression of cDNAs encoding the putative E2 ubiquitin-conjugating enzymes UbcP3, Ubc15 (ubiquitin-conjugating enzyme), or Rhp6 (Rad homolog pombe) from the strong nmt1 promoter derepressed the silent mating-type loci mat2 and mat3 and reporter genes inserted nearby. Deletion of rhp6 slightly derepressed an ade6 reporter gene placed in the mating-type region, whereas disruption of ubcP3 or ubc15 had no obvious effect on silencing. Rhp18 is the S. pombe homolog of Saccharomyces cerevisiae Rad18p, a DNA-binding protein that physically interacts with Rad6p. Rhp18 was not required for the derepression observed when UbcP3, Ubc15, or Rhp6 was overproduced. Overexpressing Rhp6 active-site mutants showed that the ubiquitin-conjugating activity of Rhp6 is essential for disruption of silencing. However, high dosage of UbcP3, Ubc15, or Rhp6 was not suppressed by a mutation in the 26S proteasome, suggesting that loss of silencing is not due to an increased degradation of silencing factors but rather to the posttranslational modification of proteins by ubiquitination. We discuss the implications of these results for the possible modes of action of UbcP3, Ubc15, and Rhp6.

scholarly journals The APC11 RING-H2 Finger Mediates E2-Dependent Ubiquitination

2000 ◽  
Vol 11 (7) ◽  
pp. 2315-2325 ◽  
Author(s):  
Joel D. Leverson ◽  
Claudio A.P. Joazeiro ◽  
Andrew M. Page ◽  
Han-kuei Huang ◽  
Philip Hieter ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
26S Proteasome ◽  
Anaphase Promoting Complex ◽  
Mitotic Progression ◽  
Protein Substrates ◽  
Ubiquitin Ligase Activity ◽  
Ubiquitin Conjugating Enzyme ◽  
Ubiquitin Conjugating Enzymes

Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). The anaphase-promoting complex or cyclosome (APC/C) comprises a multisubunit ubiquitin ligase that mediates mitotic progression. Here, we provide evidence that theSaccharomyces cerevisiae RING-H2 finger protein Apc11 defines the minimal ubiquitin ligase activity of the APC. We found that the integrity of the Apc11p RING-H2 finger was essential for budding yeast cell viability, Using purified, recombinant proteins we showed that Apc11p interacted directly with the Ubc4 ubiquitin conjugating enzyme (E2). Furthermore, purified Apc11p was capable of mediating E1- and E2-dependent ubiquitination of protein substrates, including Clb2p, in vitro. The ability of Apc11p to act as an E3 was dependent on the integrity of the RING-H2 finger, but did not require the presence of the cullin-like APC subunit Apc2p. We suggest that Apc11p is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo.

scholarly journals Opposing Effects of Ubiquitin Conjugation and SUMO Modification of PCNA on Replicational Bypass of DNA Lesions in Saccharomyces cerevisiae

2004 ◽  
Vol 24 (10) ◽  
pp. 4267-4274 ◽  
Author(s):  
Lajos Haracska ◽  
Carlos A. Torres-Ramos ◽  
Robert E. Johnson ◽  
Satya Prakash ◽  
Louise Prakash
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Lesions ◽  
Yeast Cells ◽  
Nuclear Antigen ◽  
Dependent Manner ◽  
Ubiquitin Chain ◽  
Sumo Conjugation ◽  
Ubiquitin Conjugating Enzyme ◽  
Opposing Effects ◽  
Conjugating Enzyme

ABSTRACT The Rad6-Rad18 ubiquitin-conjugating enzyme complex of Saccharomyces cerevisiae promotes replication through DNA lesions via three separate pathways that include translesion synthesis (TLS) by DNA polymerases ζ (Polζ) and Polη and postreplicational repair mediated by the Mms2-Ubc13 ubiquitin-conjugating enzyme and Rad5. Here we report our studies with a proliferating cell nuclear antigen (PCNA) mutation, pol30-119, which results from a change of the lysine 164 residue to arginine. It has been shown recently that following treatment of yeast cells with DNA-damaging agents, the lysine 164 residue of PCNA becomes monoubiquitinated in a Rad6-Rad18-dependent manner and that subsequently this PCNA residue is polyubiquitinated via a lysine 63-linked ubiquitin chain in an Mms2-Ubc13-, Rad5-dependent manner. PCNA is also modified by SUMO conjugation at the lysine 164 residue. Our genetic studies with the pol30-119 mutation show that in addition to conferring a defect in Polζ-dependent UV mutagenesis and in Polη-dependent TLS, this PCNA mutation inhibits postreplicational repair of discontinuities that form in the newly synthesized strand across from UV lesions. In addition, we provide evidence for the activation of the RAD52 recombinational pathway in the pol30-119 mutant and we infer that SUMO conjugation at the lysine 164 residue of PCNA has a role in suppressing the Rad52-dependent postreplicational repair pathway.

Evolution and expression analysis of the sorghum ubiquitin-conjugating enzyme family

2019 ◽  
Vol 46 (3) ◽  
pp. 236
Author(s):  
Liqiang Jia ◽  
QiuFang Zhao ◽  
Shu Chen
Keyword(s):  
Current Knowledge ◽  
Functional Divergence ◽  
Signalling Pathways ◽  
E3 Ligases ◽  
Ubiquitin Conjugating Enzyme ◽  
Multiple Treatments ◽  
Ubiquitin Conjugating Enzymes ◽  
Encoding Genes ◽  
Sorghum Bicolor L ◽  
Conjugating Enzyme

Ubiquitin-conjugating enzymes (UBCs), which catalyse the transfer of ubiquitin to substrate or E3 ligases, are key enzymes in ubiquitination modifications of target proteins. Current knowledge regarding the sorghum (Sorghum bicolor (L.) Moench) ubiquitin-conjugating enzyme (SbUBC) family remains very limited. We identified 53 UBC-encoding genes in the sorghum genome and divided these into 18 groups according to their phylogenetic relationship with Arabidopsis thaliana (L.) Heynh., which was further supported by conserved motif and gene structure analyses. Different expression levels under a variety of abiotic stresses suggested that these might participate in distinct signalling pathways and that they underwent functional divergence during evolution. Furthermore, several SbUBC genes responded to single treatments, and individual SbUBC genes responded to multiple treatments, suggesting that sorghum UBCs may mediate crosstalk among different signalling pathways. Overall, the results provide valuable information for better understanding the classification and putative functions of sorghum UBC-encoding genes.

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