Identification of PSME3 as a Novel Serum Tumor Marker for Colorectal Cancer by Combining Two-dimensional Polyacrylamide Gel Electrophoresis with a Strictly Mass Spectrometry-based Approach for Data Analysis

Roeßler, Markus; Rollinger, Wolfgang; Mantovani-Endl, Liliana; Hagmann, Marie-Luise; Palme, Stefan; Berndt, Peter; Engel, Alfred M.; Pfeffer, Michael; Karl, J. Philip; Bodenmüller, Heinz; Rüschoff, Josef; Henkel, Thomas; Rohr, Gerhard; Rossol, S.; Rösch, Wolfgang; Langen, Hanno; Zolg, Werner; Tacke, Michael

doi:10.1074/mcp.m600118-mcp200

Cited by 134 publications

(114 citation statements)

References 41 publications

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“…Increasing evidence has also suggested that overexpressed REGγ could positively contribute to cell cycle progression in the development of various human cancers. For instance, REGγ has been reported to be highly expressed in thyroid cancer (Okamura et al, 2003) and in colorectal cancer serum (Roessler et al, 2006). Recently, the overexpressed REGγ has been also found in human breast cancer cells and the metastatic lymph nodes (Wang et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Expression of Proteasome Activator REGγ in Human Laryngeal Carcinoma and Associations with Tumor Suppressor Proteins

Cheng²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The functional significance of the proteasome activator REGγ in the regulation of cell proliferation and apoptosis has been recognized. However, pathological contributions to tumor development remain to be elucidated. Both oncogenic proteins and tumor suppressors are targeted by REGγ for proteasomal degradation. It has been proposed that the role of the REGγ in the pathogenesis of cancer is cell-and context-specific. In this study, we aimed to explore the potential involvement of REGγ in laryngeal carcinomas, comparing protein expression in tumor and adjacent tissues by immunohistochemical staining and Western blot analysis. We also characterized the correlation between the expression of REGγ and the previously identified substrates p53 and p21. We showed that REGγ was abnormally highly expressed in cancer tissues. Statistical analysis revealed that there was a positive relationship between the level of REGγ and the expression of p53 and p21. Our study suggests that REGγ overexpression can facilitate the growth of laryngeal cancer cells.

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Section: Discussionmentioning

confidence: 99%

Expression of Proteasome Activator REGγ in Human Laryngeal Carcinoma and Associations with Tumor Suppressor Proteins

Cheng²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…troponin) at the proteomics scale, and traces back to the protohistory of proteomics 25 . The comparison between differently diseased versions of the same tissue or cell type has received brilliant recent demonstration on the search for a metastatic power associated biomarker 26 . It can be argued that such a comparison has been carried out many times, with limited success.…”

Section: A Relevant Questionmentioning

confidence: 99%

How Shall We Use the Proteomics Toolbox for Biomarker Discovery?

2007

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Biomarker discovery for clinical purposes is one of the major areas in which proteomics is used. However, despite considerable effort, the successes have been relatively scarce. In this perspective paper, we try to figure out and analyze the main causes for this limited success, and to suggest alternate strategies, which will avoid them, without eluding the foreseeable weak points of these strategies. Two major strategies are analyzed, namely the switch from body fluids to cell and tissues for the initial biomarker discovery step or, if body fluids must be analyzed, the implementation of highly selective protein selection strategies.Keywords : proteomics ; biomarkers ; plasma ; biological fluids ; cerebrospinal fluid ; Synopsis : this paper aims at stimulating discussions on how proteomics could be best used for

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“…More recently, REGγ was known to regulate p53 stability/activity in an Mdm2-dependent manner in vitro (11,12). Overexpression of REGγ has been linked to progression of some cancers (18,19). REGγ-dependent regulation of p53 prompted us to investigate whether REGγ −/− mice may display premature aging.…”

mentioning

confidence: 99%

REGγ deficiency promotes premature aging via the casein kinase 1 pathway

Zhao

Wei

et al. 2013

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

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Our recent studies suggest a role for the proteasome activator REG (11S regulatory particles, 28-kDa proteasome activator)γ in the regulation of tumor protein 53 (p53). However, the molecular details and in vivo biological significance of REGγ-p53 interplay remain elusive. Here, we demonstrate that REGγ-deficient mice develop premature aging phenotypes that are associated with abnormal accumulation of casein kinase (CK) 1δ and p53. Antibody array analysis led us to identify CK1δ as a direct target of REGγ. Silencing CK1δ or inhibition of CK1δ activity prevented decay of murine double minute (Mdm)2. Interestingly, a massive increase of p53 in REGγ −/− tissues is associated with reduced Mdm2 protein levels despite that Mdm2 transcription is enhanced. Allelic p53 haplodeficiency in REGγ-deficient mice attenuated premature aging features. Furthermore, introducing exogenous Mdm2 to REGγ −/− MEFs significantly rescues the phenotype of cellular senescence, thereby establishing a REGγ-CK1-Mdm2-p53 regulatory pathway. Given the conflicting evidence regarding the "antiaging" and "proaging" effects of p53, our results indicate a key role for CK1δ-Mdm2-p53 regulation in the cellular aging process. These findings reveal a unique model that mimics acquired aging in mammals and indicates that modulating the activity of the REGγ-proteasome may be an approach for intervention in aging-associated disorders.casein kinase 1 | PA28γ P remature aging refers to unusual acceleration of the natural aging process and is induced by multiple factors such as genetics, environment, and stress conditions. Many biological markers of premature aging have been described over the past century, including blindness, gray/yellow hair, ear atrophy, osteoporosis, lordokyphosis of the spine, reduced hair regrowth, delayed wound healing, and a shortened lifespan (1, 2). Recently, progress has been made in understanding some of the mechanisms of premature aging (3, 4). DNA damage, oxidative stress, and mitochondrial DNA (mtDNA) mutations are associated with premature aging and may be contributing agents. Furthermore, abnormalities in several cancer-related proteins such as cyclin-dependent kinase inhibitor 1 (p21), tumor protein 53 (p53), and E2F family of transcription factors (retinoblastoma-associated protein; E2F1) also are known to cause premature aging phenotypes (5-8). Given that longer lifespan is mostly associated with an increased cancer incidence, maintaining the balance between longevity and reduced risk of cancer remains a formidable task.Discrepancies between proaging and antiaging effects of p53 were observed in different experimental systems. A p53 hypermorphic mouse model that harbored a mutant p53 allele (m-p53) displayed resistance to spontaneous cancers, a shortened lifespan, and premature aging phenotypes (2). The role of p53 in promoting aging is supported by a different mouse model, in which a 44-kDa truncated naturally occurring isoform of p53 (p44 +/+ ) is expressed (7). The p44 +/+ mice displayed enhanced p53 activity and phenot...

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Identification of PSME3 as a Novel Serum Tumor Marker for Colorectal Cancer by Combining Two-dimensional Polyacrylamide Gel Electrophoresis with a Strictly Mass Spectrometry-based Approach for Data Analysis

Cited by 134 publications

References 41 publications

Expression of Proteasome Activator REGγ in Human Laryngeal Carcinoma and Associations with Tumor Suppressor Proteins

Expression of Proteasome Activator REGγ in Human Laryngeal Carcinoma and Associations with Tumor Suppressor Proteins

How Shall We Use the Proteomics Toolbox for Biomarker Discovery?

REGγ deficiency promotes premature aging via the casein kinase 1 pathway

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