UHRF2, a Ubiquitin E3 Ligase, Acts as a Small Ubiquitin-like Modifier E3 Ligase for Zinc Finger Protein 131

Oh, Yohan; Chung, Kwang Chul

doi:10.1074/jbc.m112.438234

Cited by 21 publications

(17 citation statements)

References 46 publications

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“…Finally, several other proteins have been reported as E3 enzymes although the molecular details of how they promote SUMO modification remain less clear. This class includes proteins such as Topors, UHRF2 and TIF1γ, ubiquitin E3 ligases that also promote SUMO conjugation independently of their RING domain [27][28][29], while histone deacetylases 4 [30] and 7 [31], the G-protein Rhes [32] and TRAF7 [33] have also been reported as RING domain-lacking SUMO E3s.…”

Section: Review Mattoscio and Chioccamentioning

confidence: 98%

SUMO pathway components as possible cancer biomarkers

Mattoscio

Chiocca

2015

Future Oncol.

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SUMOylation is a key post-translational modification that regulates crucial cellular functions and pathological processes. Recently, Small Ubiquitin-related MOdifier (SUMO) modification has emerged as a fundamental route that may drive different steps of human tumorigenesis. Indeed, alteration in expression or activity of one of the different SUMO pathway components may completely subvert cellular properties through fine-tuning modulation of protein(s) involved in carcinogenic pathways, leading to altered cell proliferation, apoptosis resistance and metastatic potential. Here we describe some of the most interesting findings pointing to a clear link between SUMO pathway and human malignancies. Importantly, a putative role for SUMO enzymes to predict cancer behavior can be speculated, and thus the possible application of alterations in SUMO pathway components as tumor biomarkers is discussed.

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Section: Review Mattoscio and Chioccamentioning

confidence: 98%

SUMO pathway components as possible cancer biomarkers

Mattoscio

Chiocca

2015

Future Oncol.

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“…The concept of a protein functioning as either a SUMO or ubiquitin E3 ligase is complicated by the fact that some proteins are known to function as both SUMO and ubiquitin E3 ligases, and distinguishing these enzymatic functions is often difficult (144, 167). Given the phenotypes of mouse mutants lacking the aforementioned RING and cyclin-like genes, it is evident that they play a role in the sequential paring-down process of MutSγ to MutLγ sites and/or the crossover designation process inherent within this paring-down process.…”

Section: Emerging Themes Of Crossover Controlmentioning

confidence: 99%

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

2016

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Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division. Thus, the placement, timing, and frequency of crossover formation must be exquisitely controlled. In this review, we discuss the proteins involved in crossover formation, the process of their formation and designation, and the rules governing crossovers, all within the context of the important landmarks of prophase I. We draw together crossover designation data across organisms, analyze their evolutionary divergence, and propose a universal model for crossover regulation.

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“…UHRF2 was found to interact with cyclins, CDKs, p53, pRB, PCNA, and was able to induce G1 arrest by ubiquitinating cyclins D1 and E1 (31,32). Other substrates of UHRF2 E3 Ub ligase include PCNP, nuclear aggregates containing polyglutamine repeats, hepatitis B virus core protein and zinc finger protein 131 (ZNF131) (33)(34)(35)(36). Like UHRF1, UHRF2 was also implicated in tumors; but reports about the role of UHRF2 in tumors are contradictory and uncertain.…”

Section: Uhrf2 Is a Transcription Co-regulator Formentioning

confidence: 99%

Multidimensional Proteomics Reveals a Role of UHRF2 in the Regulation of Epithelial-Mesenchymal Transition (EMT)

Lai

Liang

Chen

et al. 2016

Molecular & Cellular Proteomics

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UHRF1 is best known for its positive role in the maintenance of DNMT1-mediated DNA methylation and is implicated in a variety of tumor processes. In this paper, we provided evidence to demonstrate a role of UHRF2 in cell motility and invasion through the regulation of the epithelial-mesenchymal transition (EMT) process by acting as a transcriptional co-regulator of the EMT-transcription factors (TFs). We ectopically expressed UHRF2 in gastric cancer cell lines and performed multidimensional proteomics analyses. Proteome profiling analysis suggested a role of UHRF2 in repression of cell-cell adhesion; analysis of proteome-wide TF DNA binding activities revealed the up-regulation of many EMT-TFs in UHRF2-overexpressing cells. These data suggest that UHRF2 is a regulator of cell motility and the EMT program. Indeed, cell invasion experiments demonstrated that silencing of UHRF2 in aggressive cells impaired their abilities of migration and invasion in vitro. Further ChIP-seq identified UHRF2 genomic binding motifs that coincide with several TF binding motifs including EMT-TFs, and the binding of UHRF2 to CDH1 promoter was validated by ChIP-qPCR. Moreover, the interactome analysis with IP-MS uncovered the interaction of UHRF2 with TFs including TCF7L2 and several protein complexes that regulate chromatin remodeling and histone modifications, suggesting that UHRF2 is a transcription co-regulator for TFs such as TCF7L2 to regulate the EMT process. Taken together, our study identified a role of UHRF2 in EMT and tumor metastasis and demonstrated an effective approach to obtain clues of UHRF2 function without prior knowledge through combining evidence from multidimensional proteomics analyses. Molecular & Cellular

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UHRF2, a Ubiquitin E3 Ligase, Acts as a Small Ubiquitin-like Modifier E3 Ligase for Zinc Finger Protein 131

Cited by 21 publications

References 46 publications

SUMO pathway components as possible cancer biomarkers

SUMO pathway components as possible cancer biomarkers

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

Multidimensional Proteomics Reveals a Role of UHRF2 in the Regulation of Epithelial-Mesenchymal Transition (EMT)

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