Id proteins in cell cycle control and cellular senescence

Zebedee, Zoë; Hara, Eiji

doi:10.1038/sj.onc.1205092

Cited by 244 publications

(186 citation statements)

References 112 publications

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“…Among them, SERPINB4 had the highest overexpression with 126-fold difference from nonlesional skin. Other DEGs such as ID1, ID4, KRT16 and HMOX1, which have been previously indicated in psoriasis disease (Hanselmann et al, 2001;Leigh et al, 1995;Ronpirin et al, 2010;Ruchusatsawat et al, 2011;Zebedee et al, 2001) were also identified in the present study.…”

Section: Figsupporting

confidence: 84%

Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

Sevimoglu

Arğa

2015

OMICS: A Journal of Integrative Biology

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Computational biology and 'omics' systems sciences are greatly impacting research on common diseases such as cancer. By contrast, dermatology covering an array of skin diseases with high prevalence in society, has received relatively less attention from 'omics' and computational biosciences. We are focusing on psoriasis, a common and debilitating autoimmune disease involving skin and joints. Using computational systems biology and reconstruction, topological, modular, and a novel correlational analyses (based on fold changes) of biological and transcriptional regulatory networks, we analyzed and integrated data from a total of twelve studies from the Gene Expression Omnibus (sample size = 534). Samples represented a comprehensive continuum from lesional and nonlesional skin, as well as bone marrow and dermal mesenchymal stem cells. We identified and propose here a JAK/STAT signaling pathway significant for psoriasis. Importantly, cytokines, interferon-stimulated genes, antimicrobial peptides, among other proteins, were involved in intrinsic parts of the proposed pathway. Several biomarker and therapeutic candidates such as SUB1 are discussed for future experimental studies. The integrative systems biology approach presented here illustrates a comprehensive perspective on the molecular basis of psoriasis. This also attests to the promise of systems biology research in skin diseases, with psoriasis as a systemic component. The present study reports, to the best of our knowledge, the largest set of microarray datasets on psoriasis, to offer new insights into the disease mechanisms with a proposal of a disease pathway. We call for greater computational systems biology research and analyses in dermatology and skin diseases in general.

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Section: Figsupporting

confidence: 84%

Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

Sevimoglu

Arğa

2015

OMICS: A Journal of Integrative Biology

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“…During the early phase of TGF-␤ activation, ID3 and RGS1 were the most highly up-regulated genes in M2 IL-4/dex . ID3 is a known negative transcriptional regulator of the basic helix-loop-helix (bHLH) family that inhibits other bHLH transcription factors (42). ID3 has complex function in the immune and vascular systems including support of B cell immunity, dendritic cell differentiation, and angiogenesis (43,44).…”

Section: Discussionmentioning

confidence: 99%

Activation of a TGF-β-Specific Multistep Gene Expression Program in Mature Macrophages Requires Glucocorticoid-Mediated Surface Expression of TGF-β Receptor II

Gratchev¹,

Kzhyshkowska²,

Kannookadan³

et al. 2008

The Journal of Immunology

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Alternatively activated (M2) macrophages regulate steady state-, cancer-, and inflammation-related tissue remodeling. They are induced by Th2-cytokines and glucocorticoids (GC). The responsiveness of mature macrophages to TGF-β, a cytokine involved in inflammation, cancer, and atherosclerosis, is currently controversial. Recently, we demonstrated that IL-17 receptor B is up-regulated in human monocyte-derived macrophages differentiated in the presence of Th2 cytokines IL-4 and TGF-β1. In this study, we show that mature human macrophages differentiated in the presence of IL-4, and dexamethasone (M2IL-4/GC) but not M2IL-4 responds to TGF-β1 which induced a gene expression program comprising 111 genes including transcriptional/signaling regulators (ID3 and RGS1), immune modulators (ALOX5AP and IL-17 receptor B) and atherosclerosis-related genes (ALOX5AP, ORL1, APOC1, APOC2, and APOE). Analysis of molecular mechanism underlying GC/TGF-β cooperation revealed that surface expression of TGF-βRII was high in M2GC and M2IL-4/GC, but absent from M2IL-4, whereas the expression of TGF-βRI/II mRNA, TGF-βRII total protein, and surface expression of TGF-βRIII were unchanged. GC dexamethasone was essential for increased surface expression of functional TGF-βRII because its effect was observed also in combination with IL-13, M-CSF, and GM-CSF. Prolonged Smad2-mediated signaling observed in TGF-β1-treated M2IL-4/GC was due to insufficient activity of negative feedback mechanism what can be explained by up-regulation of SIRT1, a negative regulator of Smad7, and the retention of TGF-βRII complex on the cell surface. In summary, mature human M2 macrophages made permissive to TGF-β by GC-induced surface expression of TGF-βRII activate in response to TGF-β1, a multistep gene expression program featuring traits of macrophages found within an atherosclerotic lesion.

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“…Pathway information was derived from the Signal Transduction Knowledge Environment (stke. sciencemag.org), the Kyoto Encyclopedia of Genes and Genomes (http://www.genome.jp/kegg), and the following references: Ishitani et al, 1999;Lundberg and Weinberg, 1999;Sakamuro and Prendergast, 1999;Taguchi et al, 2000;Shaulian and Karin, 2001;Zebedee and Hara, 2001;Hyodo-Miura et al, 2002;Schneider et al, 2002;Yamagishi et al, 2002;Bracken et al, 2003;Polager and Ginsberg, 2003;Williams et al, 2003;Wu et al, 2003;Campos et al, 2004;Einarson et al, 2004;Li and Guan, 2004;Rubin and Atweh, 2004;Wada and Penninger, 2004;Sasahira et al, 2005. Of particular interest was a strong increase in the expression of WNT inhibitors in SCLC cells, namely NLK, SOX11, and TCF4.…”

Section: Regions Of Differencementioning

confidence: 99%

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Coe¹,

Lockwood²,

Girard

et al. 2006

Br J Cancer

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Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtypespecific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers.

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Id proteins in cell cycle control and cellular senescence

Cited by 244 publications

References 112 publications

Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

Activation of a TGF-β-Specific Multistep Gene Expression Program in Mature Macrophages Requires Glucocorticoid-Mediated Surface Expression of TGF-β Receptor II

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

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