Identification, tissue expression, and chromosomal position of a novel gene encoding human ubiquitin-conjugating enzyme E2-230k

Yokota, Takashi; Nagai, Hisaki; Harada, Haruhito; Mine, Nobuya; Terada, Yayoi; Fujiwara, Hiromichi; Yabe, Aya; Miyazaki, K.; Emi, Mitsuru

doi:10.1016/s0378-1119(01)00407-3

Cited by 18 publications

(19 citation statements)

References 24 publications

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“…As predicted, UBE2O is an E2 enzyme (Berleth and Pickart, 1996;Yokota et al, 2001), and a ubiquitination assay for all SMADs showed that ubiquitination of only SMAD6 and SMAD7 was altered when UBE2O was present ( Figure 2A). Because previous reports have described the polyubiquitination of SMAD7 (Koinuma et al, 2003;Zhang et al, 2012b), we investigated the novel monoubiquitination of SMAD6 by UBE2O.…”

Section: Ube2o Monoubiquitinates Smad6 In Vivosupporting

confidence: 74%

Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6

Zhang

Bauer

et al. 2013

EMBO J

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SMAD6 is a crucial feedback inhibitory regulator of bone morphogenetic protein (BMP)/SMAD signalling. Although little is known regarding the post-transcriptional modification of inhibitory SMADs and the mechanism by which their function is regulated. In this study, using a whole proteomic interaction screen for SMAD6, we identified a large putative E2 ubiquitin-conjugating enzyme UBE2O (E2-230K) as a novel interacting protein of SMAD6. We showed that UBE2O functions as an E2-E3 hybrid to monoubiquitinate SMAD6 at lysine 174 and that the cysteine 885 residue of human UBE2O is necessary for SMAD6 monoubiquitination. Inactivation of the SMAD6 monoubiquitination site specially potentiates the inhibitory ability of SMAD6 against BMP7-induced SMAD1 phosphorylation and transcriptional responses. We also found that UBE2O potentiated BMP7 signalling in a SMAD6-dependent manner. Addressing the molecular mechanism by which UBE2O and monoubiquitinated SMAD6 potentiate BMP7 signalling, we demonstrated that monoubiquitinated SMAD6 impairs the binding affinity of non-modified SMAD6 to the BMP type I receptor. Moreover, UBE2O and SMAD6 cooperated in the regulation of BMP7-induced adipogenesis.

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Section: Ube2o Monoubiquitinates Smad6 In Vivosupporting

confidence: 74%

Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6

Zhang

Bauer

et al. 2013

EMBO J

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“…Ubiquitin‐conjugating enzyme E2 O (UBE2O, UniProt accession #: Q9C0C9) is a member of the E2 family of the ubiquitin‐proteasome system (UPS). Unlike most members of this family which are about 20 to 25 kDa in molecular weight , UBE2O is unusually large, with a molecular weight of 141 kDa . UBE2O was first isolated from rabbit reticulocytes and named as E2‐230K .…”

Section: Ubiquitin‐conjugating Enzyme Ube2omentioning

confidence: 99%

Diverse roles of the E2/E3 hybrid enzyme UBE2O in the regulation of protein ubiquitination, cellular functions, and disease onset

et al. 2018

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The ubiquitin‐proteasome system is an important regulatory machinery involved in proteostasis and cellular signaling. Proteins are ubiquitinated via the concerted action of E1 ubiquitin‐activating enzymes, E2 ubiquitin‐conjugating enzymes, and E3 ubiquitin ligases. Although most of the studies to date focus on the significance of E3 ubiquitin ligases in disease development and therapeutic treatment, recent discoveries suggest that E2 ubiquitin‐conjugating enzymes might also be potential drug targets. The ubiquitin‐conjugating enzyme E2 O (UBE2O), an E3‐independent E2 (i.e. an E2/E3 hybrid enzyme), can directly mediate the ubiquitination of many substrates. These include 5′‐AMP‐activated protein kinase catalytic subunit α2 (AMPKα2), tumor suppressor ubiquitin carboxyl‐terminal hydrolase BAP1, mixed‐lineage leukemia (MLL) protein, SMAD family member 6 (SMAD6), transcription factor c‐Maf and aryl hydrocarbon receptor nuclear translocator‐like protein 1 (ARNTL or BMAL1), and free ribosomal proteins, which are ubiquitinated in distinct ways, thereby associating UBE2O with a variety of biological functions. Furthermore, UBE2O is frequently amplified or mutated in multiple cancers, and its high expression is associated with low survival rate of gastric, lung, breast, and prostate cancer patients. However, the molecular mechanisms by which UBE2O contributes to tumor initiation and progression are not fully elucidated. This review focuses on emerging insights from genetics, biochemistry, and cell biology to explore the biological functions of UBE2O and its therapeutic potential.

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“…Poly (I:C) was purchased from Invitrogen. Full-length hUBE2O [21] from cDNA of HEK293T was cloned into pCR3.1-Myc/Flag or the pLV-bc-CMV-puro lentivirus vector pLV-Myc/Flag. Full-length hTRAF6 was cloned into a pcDNA3 vector with an N-terminal Flag tag (constructed by E Meulmeester).…”

Section: Cell Culture and Plasmidsmentioning

confidence: 99%

“…UBE2O was first purified from rabbit reticulocytes and named as E2-230K [19]. It is ubiquitously expressed, but preferentially in brain, skeletal muscle and heart tissues [21]. In erythroid cells, UBE2O is upregulated during the reticulocyte stage of erythroid differentiation [22,23].…”

Section: Introductionmentioning

confidence: 99%

UBE2O negatively regulates TRAF6-mediated NF-κB activation by inhibiting TRAF6 polyubiquitination

Zhang

et al. 2013

Cell Res

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Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is a key regulator of the activation of transcription factor NF-κB by the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily. Recruitment of TRAF6 to the receptor-associated IRAK1-IRAK4-MyD88 adaptor protein complex induces lysine 63 (K63) autopolyubiquitination of TRAF6, which leads to further recruitment of downstream regulators, such as TAB2/3 and TAK1, and subsequently triggers NF-κB activation. Here, we identified the putative E2 ubiquitin-conjugating (UBC) enzyme UBE2O as a novel negative regulator of TRAF6-dependent NF-κB signaling. We found that UBE2O binds to TRAF6 to inhibit its K63-polyubiquitination, and to prevent the activation of NF-κB by IL-1β and lipopolysaccharides (LPS). We further show that the inhibitory effect of UBE2O is independent of its carboxy-terminal UBC domain. In contrast, we found that UBE2O acts to disrupt the IL-1β-induced association of TRAF6 with MyD88. These results provide novel insight into the regulation of signaling by IL-1R/TLR and TRAF6.

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Identification, tissue expression, and chromosomal position of a novel gene encoding human ubiquitin-conjugating enzyme E2-230k

Cited by 18 publications

References 24 publications

Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6

Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6

Diverse roles of the E2/E3 hybrid enzyme UBE2O in the regulation of protein ubiquitination, cellular functions, and disease onset

UBE2O negatively regulates TRAF6-mediated NF-κB activation by inhibiting TRAF6 polyubiquitination

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