Analysis of UbcH10 expression represents a useful tool for the diagnosis and therapy of astrocytic tumors

Donato, Giuseppe; Iofrida, G; Lavano, Angelo; Volpentesta, Giorgio; Signorelli, Francesco; Pallante, Pierlorenzo; Berlingieri, Maria Teresa; Pierantoni, Giovanna Maria; Palmieri, Diane; Conforti, Francesca Luisa; Maltese, Lorenza; Tucci, Luigi; Amorosi, Andrea

doi:10.5414/npp27219

Cited by 26 publications

(24 citation statements)

References 8 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have indicated that UbcH10 over-expression might be associated with the late stages of thyroid neoplastic transformation [3], and that high levels of UbcH10 correlate with most aggressive grade tumors in breast cancer [4]. Similar evidences have been found for several tumor types, such as ovarian [5], colorectal and brain cancers [6] and different lymphoma [7]. Moreover, in numerous cancer tissues the UbcH10 expression is relatively higher if compared with the adjacent nonmalignant tissues.…”

Section: Introductionsupporting

confidence: 60%

“…Moreover, in numerous cancer tissues the UbcH10 expression is relatively higher if compared with the adjacent nonmalignant tissues. All these evidences point out that the aberrant expression of UbcH10 could promote tumor expansion through dysfunction of mitotic progression, leading to deregulation of cell growth as confirmed in both thyroid [6] and breast carcinoma [8], where the interference with the UbcH10 expression significantly reduced the tumor cell proliferation. Therefore, UbcH10 appears to be a potential target for developing an anti-cancer therapy based on the suppression of its specific biological function.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structural Model of the hUbA1-UbcH10 Quaternary Complex: In Silico and Experimental Analysis of the Protein-Protein Interactions between E1, E2 and Ubiquitin

et al. 2014

View full text Add to dashboard Cite

UbcH10 is a component of the Ubiquitin Conjugation Enzymes (Ubc; E2) involved in the ubiquitination cascade controlling the cell cycle progression, whereby ubiquitin, activated by E1, is transferred through E2 to the target protein with the involvement of E3 enzymes. In this work we propose the first three dimensional model of the tetrameric complex formed by the human UbA1 (E1), two ubiquitin molecules and UbcH10 (E2), leading to the transthiolation reaction. The 3D model was built up by using an experimentally guided incremental docking strategy that combined homology modeling, protein-protein docking and refinement by means of molecular dynamics simulations. The structural features of the in silico model allowed us to identify the regions that mediate the recognition between the interacting proteins, revealing the active role of the ubiquitin crosslinked to E1 in the complex formation. Finally, the role of these regions involved in the E1–E2 binding was validated by designing short peptides that specifically interfere with the binding of UbcH10, thus supporting the reliability of the proposed model and representing valuable scaffolds for the design of peptidomimetic compounds that can bind selectively to Ubcs and inhibit the ubiquitylation process in pathological disorders.

show abstract

Section: Introductionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Structural Model of the hUbA1-UbcH10 Quaternary Complex: In Silico and Experimental Analysis of the Protein-Protein Interactions between E1, E2 and Ubiquitin

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Additionally, an overexpression of UBE2C stimulated growth and colony-forming activity in NIH3T3 cells (24). In astrocytic tumors, UBE2C gene expression has been reported to increase with advancing pathological stages (17). Therefore, UBE2C may be vital in the aggressive progression of glioma.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, the upregulation of UBE2C in brain tumors has been reported (17,18). In addition, the expression levels of UBE2C were elevated in high-grade astrocytomas, but not low-grade astrocytomas (18).…”

Section: Introductionmentioning

confidence: 99%

High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma

Kang

Zhang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Ubiquitin-conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression and is involved in the tumorigenesis of a variety of cancers. Previous studies have demonstrated that UBE2C is an important factor in the malignant progression of astrocytic tumors. However, the association between UBE2C expression and clinical prognosis of glioma patients has not been defined. In the present study, the expression of UBE2C in gliomas and non-cancerous brain tissues were detected by microarray and immunohistochemical analysis. The association between UBE2C expression and clinicopathological characteristics of the glioma patients was evaluated. The Kaplan-Meier method and multivariate Cox's proportional hazards model were used to analyze the survival time of the patients. The results demonstrated that the expression levels of UBE2C in anaplastic gliomas and glioblastoma (GBM) patients were significantly higher compared to low-grade gliomas, in microarray and immunohistochemistry analysis. A higher UBE2C expression was associated with a significantly decreased overall survival time in patients possessing anaplastic gliomas (P<0.01) and GBMs (P<0.05). Multivariate analysis of 80 GBM patients revealed that UBE2C expression was an independent prognostic factor. To the best of our knowledge, the present data suggest for the first time that UBE2C overexpression is strongly associated with an aggressive progression and poor outcome of malignant glioma. Therefore, UBE2C overexpression may be used as a predictor of poor prognosis in patients with malignant glioma.

show abstract

“…3,6 Overexpression of UBE2C at the mRNA level has been reported in a number of cancer cell lines and primary tumors, whereas only low levels were found in normal tissues. 7 The oncogenic role of UBE2C is also reported in thyroid, 8 ovarian, 9 esopha-geal, 10 breast, 11 lung, 12 liver, 13 and brain 14 tumors. Takahashi et al 15 suggest that overexpression of UBE2C may play an important role in advanced colon cancer with liver metastases and that this overexpression may be a result of chromosomal amplification at the UBE2C locus, 20q13.1.…”

mentioning

confidence: 98%

Bortezomib Stabilizes Mitotic Cyclins and Prevents Cell Cycle Progression via Inhibition of UBE2C in Colorectal Carcinoma

Bavi

Uddin

Ahmed

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Substantial evidence implicates the ubiquitin-conjugating enzyme E2C (UBE2C) gene, in several human cancers, including colorectal carcinoma (CRC). We therefore investigated the prognostic value of UBE2C alterations in CRC and UBE2C signaling in CRC cell lines. UBE2C protein expression and UBE2C gene copy number were evaluated on clinical samples by immunohistochemistry and fluorescence in situ hybridization in a TMA format. The effect of the proteasome inhibitor bortezomib and small-interfering RNA knockdown was assessed by apoptotic assays and immunoblotting. UBE2C dysregulation was associated with proliferative marker Ki-67, accumulation of cyclin A and B1, and a poor overall survival. UBE2C expression was an independent prognostic marker in early-stage (I and II) CRC. UBE2C depletion resulted in suppression of cellular growth and accumulation of cyclin A and B1. In vitro, bortezomib treatment of CRC cells caused inhibition of cell viability via down-regulation of UBE2C. UBE2C knockdown by bortezomib or transfection with specific small-interfering RNA against UBE2C also caused cells to be arrested at the G2/M level, leading to accumulation of cyclin A and cyclin B1. In vivo, a significant reduction in tumor volume and weight was noted in mice treated with a combination of subtoxic doses of oxaliplatin and bortezomib compared with treatment with oxaliplatin or bortezomib alone. Altogether, our results suggest that UBE2C and the ubiq- Although colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide, various therapeutic modalities followed in clinical practice are not life saving. More recently, advances in understanding of tumor biology have led to the development of targeted therapies, 1 allowing progress in the treatment of CRC. 2 The ubiquitin proteasome system is important for the orchestration of several important cell cycle events, such as proteolysis of cyclin-dependent kinase and their inhibitors. 3,4 Proper cell cycle progression is orchestrated by the controlled oscillation of a series of cell cycle events. Deregulation of appropriate cell cycle control often results in chromosomal instability, which is a potential trigger for the initiation of cancer. 5 In this system, substrate molecules are regulated for degradation by ubiquitinactivating enzyme (E1), ubiquitin-conjugating enzyme (E2), and E3 ligase. The ubiquitin-conjugating enzyme E2C (UBE2C), also known as UBCH10, along with the E3 ligase of the anaphase-promoting complex catalyze the ubiquitination of mitotic cyclins A and B1, as well as securin. 3,6 UBE2C is essential for cell cycle progression, and mutation of its active site cysteine confers a dominant-negative phenotype. 3,6 Overexpression of UBE2C at the mRNA level has been reported in a number of cancer cell lines and primary tumors, whereas only low levels were found in normal tissues. 7 The oncogenic role of UBE2C is also reported in thyroid, 8 ovarian, 9 esopha-

show abstract

Analysis of UbcH10 expression represents a useful tool for the diagnosis and therapy of astrocytic tumors

Cited by 26 publications

References 8 publications

Structural Model of the hUbA1-UbcH10 Quaternary Complex: In Silico and Experimental Analysis of the Protein-Protein Interactions between E1, E2 and Ubiquitin

Structural Model of the hUbA1-UbcH10 Quaternary Complex: In Silico and Experimental Analysis of the Protein-Protein Interactions between E1, E2 and Ubiquitin

High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma

Bortezomib Stabilizes Mitotic Cyclins and Prevents Cell Cycle Progression via Inhibition of UBE2C in Colorectal Carcinoma

Contact Info

Product

Resources

About