Clinicopathological relevance of UbcH10 in breast cancer

Fujita, Takeo; Ikeda, Hirokuni; Kawasaki, K.; Taira, Naruto; Ogasawara, Yuki; Nakagawara, Akira; Doihara, Hiroyoshi

doi:10.1111/j.1349-7006.2008.01026.x

Cited by 25 publications

(18 citation statements)

References 42 publications

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“…We believe it is more likely that even low levels of UbcH10 support initiation of short chains, which could then be extended by Ube2S. In support of this notion, mutation of UbcH10 in flies or its efficient depletion in several human cell lines lead to cyclin B stabilization and a delay in mitosis (21,23,26,(35)(36)(37), while incomplete depletion of UbcH10 does not produce these phenotypes (38). Consistent with their close cooperation in modifying APC/C substrates, UbcH10 and Ube2S are tightly co-regulated in cells.…”

Section: Discussionmentioning

confidence: 81%

Identification of a physiological E2 module for the human anaphase-promoting complex

Williamson

Wickliffe

Mellone

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

270

380

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Ubiquitination by the anaphase-promoting complex (APC/C) is essential for proliferation in all eukaryotes. The human APC/C promotes the degradation of mitotic regulators by assembling K11-linked ubiquitin chains, the formation of which is initiated by its E2 UbcH10. Here, we identify the conserved Ube2S as a K11-specific chain elongating E2 for human and Drosophila APC/C. Ube2S depends on the cell cycledependent association with the APC/C activators Cdc20 and Cdh1 for its activity. While depletion of Ube2S already inhibits APC/C in cells, the loss of the complete UbcH10/Ube2S-module leads to dramatic stabilization of APC/C substrates, severe spindle defects, and a strong mitotic delay. Ube2S and UbcH10 are tightly co-regulated in the cell cycle by APC/C-dependent degradation. We conclude that UbcH10 and Ube2S constitute a physiological E2-module for APC/C, the activity of which is required for spindle assembly and cell division.K11-linked chain ͉ proteasome ͉ ubiquitin

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Section: Discussionmentioning

confidence: 81%

Identification of a physiological E2 module for the human anaphase-promoting complex

Williamson

Wickliffe

Mellone

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

270

380

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“…For hTERT expression, an intensity score of ≥2 and ≥11% of cells with positive hTERT staining was considered to indicate high expression, and an intensity score of <2 or <11% of cells with hTERT positive staining was considered to indicate low expression (21). By contrast, UBE2D3 protein expression levels were classified as high when UBE2D3 staining was present in >50% of cells (22). Expression in the cytoplasm and nucleus was regarded as an indication of positive expression for the two proteins (22,23).…”

Section: Methodsmentioning

confidence: 99%

“…By contrast, UBE2D3 protein expression levels were classified as high when UBE2D3 staining was present in >50% of cells (22). Expression in the cytoplasm and nucleus was regarded as an indication of positive expression for the two proteins (22,23). Using this method, the expression of hTERT and UBE2D3 was detected in 150 esophageal cancer and 30 adjacent tissue samples.…”

Section: Methodsmentioning

confidence: 99%

UBE2D3 is a positive prognostic factor and is negatively correlated with hTERT expression in esophageal cancer

Guan¹,

Wang²,

Lei³

et al. 2015

Oncology Letters

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Human telomerase reverse transcriptase (hTERT) is a critical factor in unlimited cell proliferation and immortalization, with numerous studies demonstrating that high expression of hTERT is a poor prognostic factor in various types of cancer. Ubiquitin-conjugating enzyme E2D 3 (UBE2D3) is a member of the E2 family, and participates in the ubiquitin proteasome pathway to regulate basic cellular activities, such as cell cycle control, the DNA damage response, apoptosis, and tumorigenesis. Our previous study initially determined that downregulation of UBE2D3 expression increases hTERT expression and cell proliferation, however, the association between the expression of these two proteins and their functions in cancer tissues remains unknown. Therefore, the protein expression levels of hTERT and UBE2D3 were evaluated in 150 esophageal cancer and 30 adjacent healthy tissue samples by performing immunohistochemical analysis. Concurrently, the clinicopathological data of the enrolled patients were obtained to allow correlation analysis. It was identified that the expression of hTERT in the esophageal cancer tissues was significantly higher compared with that of the adjacent tissues (P=0.015), however, the expression of UBE2D3 was significantly lower in esophageal cancer tissues than the adjacent tissues (P=0.001). Additionally, the study demonstrated that hTERT was significantly upregulated in poorly-differentiated, advanced tumor-node-metastasis (TNM) stage cancer tissues (P<0.05 for all), however, UBE2D3 expression was downregulated in poorly-differentiated, lymph node invaded cancer tissues and recurrent cases. It was also identified that traditional factors, including tumor location, T stage, lymph node status, TNM stage, and molecular factors of hTERT and UBE2D3, were significantly associated with overall survival time (P<0.05 for all). Furthermore, UBE2D3, lymph node status and tumor location were independent prognostic factors for esophageal cancer in multivariate analysis. Most notably, hTERT and UBE2D3 expression were negatively correlated with each other. In conclusion, the findings of the present study indicated that hTERT and UBE2D3 proteins appear to be involved in the development of esophageal cancer, that UBE2D3 may a positive prognostic factor for esophageal cancer, and that UBE2D3 and hTERT expression levels are inversely correlated.

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“…Recently, it was shown that anaphase-promoting complex (APC), the key ubiquitin E3 ligase that governs cell cycle progression is localized to the basal body of the motile cilia in multiciliated Xenopus epidermal cells, where it has some role in regulating ciliary polarity (Ganner et al, 2009). In mitosis, APC sequentially recruits co-activators (Cdc20 followed by Cdh1) and cooperates with two specific E2s (UBCH10 and Ube2S) to control proteolysis of key regulators of the metaphase to anaphase transition (Fujita et al, 2009; Fujita et al, 2009). APC also has a less well understood role in regulating other cellular processes, such as neurogenesis, metabolism, and myogenesis (Kim et al, 2009; Eguren et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium

Wang

Kirschner

2014

eLife

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The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anaphase-promoting complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal microtubules in the primary cilium. Furthermore, the metaphase APC co-activator, Cdc20, is specifically recruited to the basal body of primary cilia. Inhibition of APC-Cdc20 activity increases the ciliary length, while overexpression of Cdc20 suppresses cilium formation. APC-Cdc20 activity is required for the timely resorption of the cilium after serum stimulation. In addition, APC regulates the stability of axonemal microtubules through targeting Nek1, the ciliary kinase, for proteolysis. These data demonstrate a novel function of APC beyond cell cycle control and implicate critical role of ubiquitin-mediated proteolysis in ciliary disassembly.DOI: http://dx.doi.org/10.7554/eLife.03083.001

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Clinicopathological relevance of UbcH10 in breast cancer

Cited by 25 publications

References 42 publications

Identification of a physiological E2 module for the human anaphase-promoting complex

Identification of a physiological E2 module for the human anaphase-promoting complex

UBE2D3 is a positive prognostic factor and is negatively correlated with hTERT expression in esophageal cancer

The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium

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