Ugene, a Newly Identified Protein That Is Commonly Overexpressed in Cancer and Binds Uracil DNA Glycosylase

Guo, Chunguang; Zhang, Xiaodong; Fink, Stephen P.; Platzer, Petra; Wilson, Keith E.; Willson, James K.V.; Wang, Benlian; Markowitz, Sanford D.

doi:10.1158/0008-5472.can-08-1259

Cited by 40 publications

(36 citation statements)

References 16 publications

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“…While our current emphasis is focused on FAM72A (Ugene), it is uncertain, at present, as to whether additional members of the FAM72 family are functionally divergent or show similar function to LMPIP (Ugene, FAM72A), which awaits further studies. Also, the results from our current studies of LMP1-induced Ugene in the context of EBV infection and NPC are at variance with those found in the original discovery of Ugene (Guo et al, 2008). The reasons for this difference are currently unknown, but it is tempting to speculate that the different results may be the result of our emphasis on the initial steps in the induction of Ugene expression and function as a consequence of EBV infection or LMP1 overexpression, rather than being on the 'stationary' phase in the existing tumor cells.…”

Section: Discussioncontrasting

confidence: 94%

“…Interestingly, Guo et al (2008) showed that Ugene-encoded protein is localized in the nucleus and interacts with uracil DNA glycosylase 2, a base excision repair enzyme involved in DNA repair pathways, the alteration of which has often been noted in cancers. These results suggested the potential involvement of Ugene in tumorigenesis; however, as the investigators noted, when tested in epithelial or fibroblasts, no oncogenic activity of Ugene could be demonstrated and no apparent influence on the regulation of uracil DNA glycosylase 2 repair activity was found in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Ugene, a binding partner of uracil DNA glycosylase, has been recently found to be an overexpressed protein in many kinds of cancers (Guo et al, 2008), and suggested to have a role in tumor formation and promotion, but its cellular function and oncogenic activity are still unclear. In the initial screenings of LMP1-targeted genes in LMP1-transfected NPC cells, Ugene was identified to be highly inducible by LMP1, and hence designated herein as LMP1-induced protein (LMPIP).…”

Section: Introductionmentioning

confidence: 99%

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Functional interaction of Ugene and EBV infection mediates tumorigenic effects

et al. 2011

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Epstein-Barr virus (EBV) infection is associated with many human neoplasms, in which EBV-derived latent membrane protein-1 (LMP1) appears to be critical, but its exact oncogenic mechanism remains to be defined. To this end, our initial microarray analyses identified a LMP1-inducible gene, Ugene, originally characterized as a binding partner for uracil DNA glycosylase 2, which is highly expressed in malignant colon cancer. In this report, it was found that Ugene, designated herein as LMP1-induced protein (LMPIP), was induced, in a time-dependent manner, in EBV-infected peripheral blood mononuclear cells and LMP1-transfected 293 cells. Functionally, when compared with mock-transfected cells, overexpression of LMPIP in nasopharyngeal carcinoma (NPC) cell lines resulted in a decrease in reactive oxygen species production and maintained mitochondria membrane potential (Dw) loss induced by H 2 O 2 . The NPC cells transfected with LMPIP also showed a decrease in G1 population and an increase in the cell population in sub-G1 and multiploid phase, concomitant with increased levels of cell cycle activators, including cyclin D1 and CDK4. In contrast, silencing of LMPIP expression in the NPC tumor cell lines with short hairpin RNA interference revealed significantly decreased cell population at G1/S phase, while the number of cells in multiploid phase increased. Significantly, NPC cells with LMPIP knock-down also showed a decrease in tumorigenic and transforming activity induced by ectopic LMP1 expression, as determined by analyses of soft agar foci and tumor size in nude mice. Further, elevated LMPIP expression was also noted in cytoplasm and nuclei in EBVinfected NPC tumor cell mass and non-EBV-infected tumor cell lines. These results suggested that LMPIP may have an important mediator role in EBV-mediated neoplasm and may serve as a new target for therapy of tumors induced by EBV infection.

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Section: Discussioncontrasting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional interaction of Ugene and EBV infection mediates tumorigenic effects

et al. 2011

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“…Lead discovery by protein-ligand-binding-site prediction Since FAM72A plays a significant role in tumorigenesis [3,4], the present study on the theoretical 3D protein structure modeling of FAM72A led us to search for a potential ligandbinding site of FAM72A as the identification of proteinligand-binding sites is a decisive pathway for the elucidation of protein function and development of therapeutics. A metaserver approach (e.g., via http://zhanglab.ccmb.med.umich.…”

Section: Protein Structure Evaluationmentioning

confidence: 99%

“…Using these methods, we discovered the new membrane-bound FAM72A protein (also known as p17, Ugene, or LMPIP) with demonstrated highly promising clinical relevance to survival/ death outcomes in patients with various kinds of cancers, as it can be linked to tumorigenic effects in non-neuronal tissues [2][3][4]. Our group also unraveled FAM72A's mode of action, and our data demonstrate that FAM72A interacts with various tumor suppressor proteins that are (epi-) genetically modified in cancer [3] and thus, interference with FAM72A's activities might be a novel option to influence the tumor suppressor protein p53 signaling pathways for the treatment of tumors.…”

Section: Introductionmentioning

confidence: 99%

Lead discovery and in silico 3D structure modeling of tumorigenic FAM72A (p17)

2014

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FAM72A (p17) is a novel neuronal protein that has been linked to tumorigenic effects in non-neuronal tissue. Using state of the art in silico physicochemical analyses (e.g., I-TASSER, RaptorX, and Modeller), we determined the three-dimensional (3D) protein structure of FAM72A and further identified potential ligand-protein interactions. Our data indicate a Zn(2+)/Fe(3+)-containing 3D protein structure, based on a 3GA3_A model template, which potentially interacts with the organic molecule RSM ((2s)-2-(acetylamino)-N-methyl-4-[(R)-methylsulfinyl] butanamide). The discovery of RSM may serve as potential lead for further anti-FAM72A drug screening tests in the pharmaceutical industry because interference with FAM72A's activities via RSM-related molecules might be a novel option to influence the tumor suppressor protein p53 signaling pathways for the treatment of various types of cancers.

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The pan‐cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target

Hirachan

Shen

et al. 2023

Environmental Toxicology

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In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameter's relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2/M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.

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Ugene, a Newly Identified Protein That Is Commonly Overexpressed in Cancer and Binds Uracil DNA Glycosylase

Abstract: Expression microarrays identified a novel transcript, designated as Ugene, whose expression is absent in normal colon and colon adenomas, but that is commonly induced in malignant colon cancers. These findings were validated by real-time PCR

Cited by 40 publications

References 16 publications

Functional interaction of Ugene and EBV infection mediates tumorigenic effects

Functional interaction of Ugene and EBV infection mediates tumorigenic effects

Lead discovery and in silico 3D structure modeling of tumorigenic FAM72A (p17)

The pan‐cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target

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