Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia, meiosis, and cancer may meet in the nucleus

Shakib, Kaveh; Norman, Jill T.; Fine, Leon G.; Brown, L. R.; Godovac‐Zimmermann, Jasminka

doi:10.1002/pmic.200401108

Cited by 38 publications

(40 citation statements)

References 167 publications

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“…Similarly, D'Mello and Galli (33) reported that Rp8 mRNA was not induced in neuronal apoptosis triggered in a culture system by nerve growth factor deprivation. Recently, proteomic methodology was used to study proteins in rat kidney fibroblasts during prolonged hypoxia (34). In this study, Rp8 levels were found to increase at least 2-fold in cells subjected to 1% oxygen for a 12-h period.…”

Section: Discussionmentioning

confidence: 89%

Repression of thePDCD2gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas

Baron¹,

Zeleznik‐Le

Baron

et al. 2007

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

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The human BCL6 gene on chromosome 3 band q27, which encodes a transcriptional repressor, is implicated in the pathogenesis of human lymphomas, especially the diffuse large B-cell type. We previously identified the human PDCD2 (programmed cell death-2) gene as a target of BCL6 repression. PDCD2 encodes a protein that is expressed in many human tissues, including lymphocytes, and is known to interact with corepressor complexes. We now show that BCL6 can bind directly to the PDCD2 promoter, repressing its transcription. Knockdown of endogenous BCL6 in a human B cell lymphoma line by introduction of small interfering RNA duplexes increases PDCD2 protein expression. Furthermore, there is an inverse relationship between the expression levels of the BCL6 and PDCD2 proteins in the lymphoid tissues of mice overexpressing human BCL6 (high BCL6 levels, minimal PDCD2) and controls (minimal BCL6, high PDCD2) as well as in tissues examined from some human B and T cell lymphomas. These data confirm PDCD2 as a target of BCL6 and support the concept that repression of PDCD2 by BCL6 is likely important in the pathogenesis of certain human lymphomas.human lymphomas ͉ target of BCL6 B CL6, a gene on chromosome 3, band q27, encodes a nuclear zinc finger protein that is a transcriptional repressor (1-3). This protein is expressed at high levels in human lymph node germinal center B cells, most cortical thymocytes, and some human B and T cell lymphomas (4). The BCL6 gene was identified (5-7) through its involvement in chromosomal translocations that occur in Ϸ40% of diffuse large-cell B cell lymphomas. In other lymphomas, mutations occur 5Ј to the BCL6 coding region (8). The BCL6 protein binds DNA in a sequencespecific fashion through its C-terminal zinc finger region (9, 10). It conveys transcriptional repression through an N-terminal POZ domain and a second domain that is more centrally located (1-3, 11) and interacts with a number of corepressors (12)(13)(14). It is thought that the BCL6-repressive effects are mediated through multiprotein repression complexes with histone deacetylase activity. A peptide that specifically binds BCL6 and blocks corepressor recruitment leads to apoptosis and cell-cycle arrest of BCL6-positive lymphoma cells (15). Mice overexpressing human (16) or murine (17) BCL6 develop lymphomas.We previously generated a dominant-negative cell system (18) with the use of a construct expressing the BCL6 zinc fingers, which compete with the binding of endogenous BCL6 in BJAB cells (an Epstein-Barr virus-negative Burkitt lymphoma cell line expressing high levels of BCL6) (19). Because BCL6 is a repressor, competition for binding of the full-length endogenous BCL6 protein by the exogenously transfected zinc fingers results in up-regulation of BCL6 target genes. We used subtractive hybridization techniques to amplify differentially expressed sequences. These studies led to the identification of the PDCD2 (programmed cell death-2) gene as a target of BCL6. Immunohistochemistry performed on human tonsil with antibodies sp...

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Section: Discussionmentioning

confidence: 89%

Repression of thePDCD2gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas

Baron¹,

Zeleznik‐Le

Baron

et al. 2007

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

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“…Furthermore hypoxia causes dynamic changes in protein subcellular location involving functions that go far beyond changes in glycolysis and include TCA-cycle, OxPhos and chromatin remodeling proteins among many others. 42,71 Several years ago we demonstrated that numerous glycolytic enzymes translocate to the nucleus under hypoxia 71 -the present results suggest that similar dynamic subcellular distributions may be operative for other functional systems such as oxidative phosphorylation and the TCA-cycle and may contribute to cancer and other diseases.…”

Section: Potential Connections To Cancermentioning

confidence: 97%

“…GAPDH, PGAM1, PKM2 and LADH were changed by hypoxia. 71 In recent years participation of ENO1, FBP1, GAPDH, PKM2 and LADH in transcription in the nucleus has been demonstrated by others (Supporting Information Table 5). Very recently, connections to the cell cycle have been established for nuclear FBP1 72 and PGAM1 in the nucleus of cancer cells has been observed.…”

Section: Proteins Involved In Glycolysismentioning

confidence: 99%

Spatial Distribution of Cellular Function: The Partitioning of Proteins between Mitochondria and the Nucleus in MCF7 Breast Cancer Cells

et al. 2012

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“…SYCP2 is part of the synaptonemal complex involved in forming lateral elements and cross bridges that contribute to pairing of sister chromatids during meiosis and probably are involved in the interaction between chromatin and nuclear envelope. 59 There is evidence that HPV infection in cervical cells promotes morphological changes in the nuclear membrane as well as condensation of chromatin attached to the inner part of the nuclear membrane. 60 Thus, it is possible that SYCP2 may be involved in chromatin-nuclear envelope interactions in HPV-positive SCCHN.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas

Martínez

Wang

Hobson

et al. 2007

European Journal of Cancer

174

138

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Human papillomaviruses (HPVs) have been implicated in the pathogenesis of a subset of squamous cell carcinoma of the head and neck (SCCHN). The goal of this study was to compare the cellular gene expression profiles of HPV-positive and HPV-negative oropharyngeal carcinomas with those of the normal oral epithelium. Using Affymetrix Human U133A GeneChip, our results showed that 397 genes were differentially expressed in HPV-positive SCCHN compared to the normal oral epithelium. The up-regulated genes included those involved in cell cycle regulation (CDKN2A), cell differentiation (SFRP4) and DNA repair (RAD51AP1), while the down-regulated genes included those involved in proteolysis (PRSS3). We also found 162 differentially expressed genes in HPVnegative SCCHN compared to the normal oral mucosa. The up-regulated genes included those involved in cell proliferation (AKR1C3) and transcription regulation (SNAPC1), while downregulated genes included those involved in apoptosis (CLU) and RNA processing (RBM3). Our studies also identified a subgroup of 59 differentially expressed genes in HPV-positive SCCHN as compared to both HPV-negative SCCHN and normal oral tissues. Such up-regulated genes included those involved in nuclear structure and meiosis (SYCP2), DNA repair (RFC5), and transcription regulation (ZNF238). Genes involved in proteolysis (KLK8) and signal transduction (CRABP2) were found to be down-regulated in HPV-positive SCCHN. The results of GeneChip experiments were validated by quantitative real-time RT-PCR analysis of a few representative genes. Our results reveal specific gene expression patterns in HPV-positive and HPV-negative oropharyngeal squamous carcinomas that may serve as potential biomarkers for the development of SCCHN. Novelty and impact of the paper: Using a 22,200 human transcript oligonucleotide microarray platform, we have examined the gene expression profiles in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas as compared to the normal oropharyngeal mucosa. Our study has identified several new genes whose expression is specifically associated with the presence of HPV-16 in the oropharyngeal squamous mucosa. Furthermore, we have identified several genes whose expression is altered in HPVnegative SCCHN as compared to the normal oral mucosa. Results of our study could contribute to the understanding of pathogenic mechanisms involved in the development of HPV-positive and HPV-negative oropharyngeal cancers and consequently in the identification of potential biomarkers associated with these two subtypes of squamous cell carcinomas.

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Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia, meiosis, and cancer may meet in the nucleus

Cited by 38 publications

References 167 publications

Repression of thePDCD2gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas

Repression of thePDCD2gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas

Spatial Distribution of Cellular Function: The Partitioning of Proteins between Mitochondria and the Nucleus in MCF7 Breast Cancer Cells

Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas

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