Abstract:
:The ubiquitin-proteasome pathway is fundamental to synchronized continuation of many cellular processes, for example, cell-cycle progression, stress response, and cell differentiation. Recent studies have shown that the ubiquitin-proteasome pathway functions in the regulation of nucleotide excision repair (NER) in yeast. In order to investigate the role of the ubiquitin-proteasome pathway in the NER of mammalian cells, global genomic repair (GGR), and transcription-coupled repair (TCR) were examined in a mouse ts20 cell line that harbors a temperature-sensitive ubiquitin-activating enzyme (E1). We found that E1 inactivation-induced ubiquitination deficiency decreased both GGR and TCR, indicating that the ubiquitination system is involved in the optimization of entire NER machinery in mammalian cells. We specifically inhibited the function of 19S proteasome subunit by overexpressing 19S regulatory complex hSug1 or its mutant protein hSug1mk in repair competent human fibroblast, OSU-2, cells and compared their capacity for NER. The results showed that 19S regulatory complex positively modulates NER in cells. In addition, we treated OSU-2 cells with the inhibitors of 20S subunit function, MG132 and lactacystin, and demonstrated that the catalytic activity of 20S subunit is also required for efficient NER. Moreover, the UV-induced recruitment of repair factor xeroderma pigmentosum protein C (XPC) to damage sites was negatively affected by treatment of repair competent cells with MG132. Taken together, we conclude that the ubiquitin-proteasome pathway has a positive regulatory role for optimal NER capacity in mammalian cells and appears to act through facilitating the recruitment of repair factors to DNA damage sites.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Wang QE,Wani MA,Chen J,Zhu Q,Wani G,El-Mahdy MA,Wani AAdoi
10.1002/mc.20065subject
Has Abstractpub_date
2005-01-01 00:00:00pages
53-64issue
1eissn
0899-1987issn
1098-2744journal_volume
42pub_type
杂志文章abstract::Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we reported that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) [Oncogene, 2010, 29: 5241-5253]. In general, various studies established inhibition of cell proliferation by SPRY in cancer. The mechanisms by which SPRY regulates c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22379
更新日期:2016-09-01 00:00:00
abstract::We evaluated whether high-fat diet (HFD), in the absence of increased calorie intake, increases colon cancer growth and metastasis. Four-week-old male BALB/c mice were fed on an HFD (60 kcal% fat) or control diet (10 kcal% fat) for 16 wk, after which CT26 colon cancer cells were subcutaneously injected into the right ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20856
更新日期:2012-11-01 00:00:00
abstract::The growth hormone receptor (GHR) and growth hormone-binding protein (GH-BP) expression were characterized in liver nodules and hepatomas from male Wistar rats. The mRNA levels of GHR and GH-BP, studied by northern blot analysis and solution hybridization, were 35-50% (in nodules) and 2-6% (in hepatomas) of the level ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940030309
更新日期:1990-01-01 00:00:00
abstract::Cancer cells mainly rely on glycolysis for energetic needs, and mitochondrial ATP production is almost inactive. However, cancer cells require the integrity of mitochondrial functions for their survival, such as the maintenance of the internal membrane potential gradient (DeltaPsim). It thus may be predicted that Delt...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20539
更新日期:2009-08-01 00:00:00
abstract::Prostate cancer (PCA) is the second most malignancy in American men. Advanced stage PCA cells possess unlimited replication potential as well as resistance to apoptosis. Therefore, targeting survival mechanisms and activating apoptotic machinery in PCA cells using nontoxic phytochemicals is suggested as an attractive ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20670
更新日期:2010-10-01 00:00:00
abstract::Recent evidence suggests that the A allele of the ornithine decarboxylase (ODC) gene is a genetic risk factor for prostate cancer. ODC is a target gene of the highly polymorphic androgen receptor (AR) gene, short alleles of which have been associated in some studies with increased prostate cancer risk. We determined O...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20047
更新日期:2004-10-01 00:00:00
abstract::Hepatitis B virus (HBV) X protein (HBx) and cyclooxygenase-2 (COX-2) are all playing roles in hepatocellular carcinoma (HCC), but the reversing effects of COX-2 inhibitors on the neoplastic features caused by HBx protein is still unclear. To further evaluate the therapeutic potential of celecoxib on HBx mediated trans...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20455
更新日期:2009-01-01 00:00:00
abstract::Ezrin is known to regulate cellular survival, adhesion, migration, and invasion and has been identified as one of the key components of tumor progression and metastasis. The authors investigated ezrin expression in human hepatocellular carcinoma (HCC) and sought to determine its relation with clinicopathologic paramet...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20653
更新日期:2010-09-01 00:00:00
abstract::Mutational activation of RAS proteins occurs in nearly 30% of all human tumors. To date direct pharmacological inhibition of RAS oncoproteins has not been possible. As a consequence, current strategies are focusing on the development of inhibitors that target those kinases acting downstream of RAS proteins, including ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20555
更新日期:2009-11-01 00:00:00
abstract::The abnormal expression of adipocyte enhancer binding protein 1 (AEBP1) has been implicated in the carcinogenesis and progression of various types of human tumors. However, the role of AEBP1 in colon adenocarcinoma (COAD) remains largely unelucidated. In this study, we explored the clinical significance and biological...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23066
更新日期:2019-10-01 00:00:00
abstract::To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor-associated macrophages (TAMs). The migration ability of RAW264.7 macrophages was determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22936
更新日期:2019-03-01 00:00:00
abstract::Benzo[alpha]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), the major metabolite of benzo[a]pyrene (B[a]P), shows an ultimate complete carcinogen in various animals and is a causative agent for human cancers. However, its effects on the activation of signal pathways and the expression of genes involved in its carcinogenic eff...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20260
更新日期:2007-01-01 00:00:00
abstract::Betanin, also called beetroot red, has been extensively used as a food colorant. In this study, the chemopreventive activity of betanin by oral consumption was investigated in two mouse lung tumor models. Vinyl carbamate (VC) and benzo(a)pyrene (B(a)P) were used to induce lung tumors, and female A/J mice were treated ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21907
更新日期:2013-09-01 00:00:00
abstract::DNA hypermethylation is associated with decreased expression of tumor suppressor genes. We previously observed decreased Fhit expression and Fhit promoter region hypermethylation in rodent tumors induced by various carcinogens, and noted that the 5' regulatory regions in the promoter, exon 1, and intron 1 were differe...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20100
更新日期:2005-07-01 00:00:00
abstract::The atomic bombing of Hiroshima and Nagasaki and the nuclear accident at Chernobyl raised the question of prenatal sensitivity to ionizing radiation-induced cancer. In this study, mice were exposed to single doses of gamma-radiation (0.2-2.0 Gy) at different embryonic stages. The tumor incidence increased with dose fr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor in the gastrointestinal tract. Prostate cancer associated transcript 6 (PCAT6) is a long noncoding RNA (lncRNA) and plays a pivotal role in tumor formation. Present study was designed to explore the function of PCAT6 in GIST. Ki67 staining, colony for...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23199
更新日期:2020-06-01 00:00:00
abstract::Patulin (PAT), a present day major contaminant of commercial apple and apple products is reported to be carcinogenic, embryotoxic, and immunotoxic. While oral and inhalation are considered to be the most prevalent routes of exposure to this toxin, exposure through skin is now being extensively investigated. Our previo...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22060
更新日期:2014-12-01 00:00:00
abstract::Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22069
更新日期:2015-01-01 00:00:00
abstract::Cytokines are considered to play an important role in tumor pathogenesis and progression, and recent studies have demonstrated that a variety of forms, including interleukins (ILs) and transforming growth factor-beta(s) (TGF-beta(s)), may regulate tumors. In the present study, the expression of TGF-beta isoforms and I...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract::The metalloproteinase matrilysin is widely expressed in the epithelial tumor cells of malignant colorectal adenocarcinomas. Approximately 50% of benign adenomas also express low levels of matrilysin that is focally localized. The expression of stromelysin-1, stromelysin-3, and gelatinase A was observed in the stromal ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940100404
更新日期:1994-08-01 00:00:00
abstract::The Ron receptor tyrosine kinase is overexpressed in approximately half of all human colon cancers. Increased Ron expression positively correlates with tumor progression, and reduction of Ron levels in human colon adenocarcinoma cells reverses their tumorigenic properties. Nearly all colon tumors demonstrate loss of t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20551
更新日期:2009-11-01 00:00:00
abstract::An in vitro model system for xenogenization has been developed in which an immunogenic, nonmalignant phenotype was selected from a highly malignant T-cell line (S49). We showed by single-strand conformation polymorphism and DNA sequence analysis that specific point mutations in the p53 tumor suppressor gene correlated...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940080404
更新日期:1993-01-01 00:00:00
abstract::To explore the mechanisms underlying the chemopreventive effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in prostate cancer, we evaluated the anti-proliferative and apoptosis-inducing effects of 4-HPR in the androgen-sensitive human prostate cancer cell line LNCaP. 4-HPR decreased the number of...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199903)24:3<160::aid-mc2>3
更新日期:1999-03-01 00:00:00
abstract::microRNAs (miRNAs) are commonly altered in glioblastoma. Publicly available algorithms suggest the Wnt pathway is a potential target of miR-577 and the Wnt pathway is commonly altered in glioblastoma. Glioblastoma has not been previously evaluated for miR-577 expression. Glioblastoma tumors and cell lines were evaluat...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22304
更新日期:2016-05-01 00:00:00
abstract::There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these mole...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22503
更新日期:2017-02-01 00:00:00
abstract::Mutations in RB and PTEN are linked to castration resistance and poor prognosis in prostate cancer. Identification of genes that are regulated by these tumor suppressors in a context that recapitulates cancer progression may be beneficial for discovering novel therapeutic targets. Although various genetically engineer...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22444
更新日期:2016-12-01 00:00:00
abstract::Increasing evidence from recent research suggests a connection between cancer and a deranged equilibrium of histone acetylation, which is maintained by two competing enzymatic activities, histone acetyltransferases (HATs) and histone deacetylases (HDACs). It is our hypothesis that a significant proportion of leukemias...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(200004)27:4<268::aid-mc4>3
更新日期:2000-04-01 00:00:00
abstract::Dishevelled-3 (Dvl-3) and p120-catenin (p120ctn) have abnormal expression in non-small cell lung cancer (NSCLC), which is associated with poor prognosis. Dvl-3 upregulates p120ctn transcription in NSCLC cells, but the mechanism is unknown. Here we transiently transfected Dvl-3 cDNA to NSCLC cells. Dvl-3 transfection i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22196
更新日期:2015-06-01 00:00:00
abstract::Mice with conditional gene deletions have been extremely valuable in allowing investigators to study the genes of interest in a tissue-specific manner. The Cre-loxP recombination system provides a powerful tool to produce targeted rearrangements of particular genes. The keratin 5-Cre recombinase (K5Cre) transgenic mou...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20192
更新日期:2007-01-01 00:00:00
abstract::In tumor cells that have lost responsiveness to the growth inhibitory effects of transforming growth factor beta (TGFbeta), increased TGFbeta production by the tumor cells often contributes to cancer progression, primarily through paracrine mechanisms. Here we investigated the major components of the activator protein...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20189
更新日期:2006-08-01 00:00:00