Methylation of SOCS-3 and SOCS-1 in the carcinogenesis of Barrett's adenocarcinoma

Tischoff, Iris; Hengge, Ulrich R.; Vieth, Michael; Ell, Christian; Stolte, Manfred; Weber, Anette; Schmidt, Wolfgang E.; Tannapfel, Andrea

doi:10.1136/gut.2006.111633

Cited by 83 publications

(45 citation statements)

References 33 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…24 Finally, hypermethylation of SOCS3 promoter has been demonstrated in a number of malignancies. [31][32][33][34]57 We detected SOCS3 promoter methylation in 32% (16/50) of patients with IMF but not in patients with PV, ET or myelofibrosis preceded by another MPD. Hence, epigenetic modification of SOCS3 represents a novel mechanism by which JAK/STAT signaling may become aberrant within MPD.…”

Section: Discussionmentioning

confidence: 74%

“…Methylation of the SOCS3 promoter and reduced gene expression have been detected in patients with lung cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma and Barrett's adenocarcinoma. [31][32][33][34] We, therefore, wanted to investigate the contribution, if any, of aberration(s) of SOCS1 and SOCS3 in the pathogenesis of MPD. A large cohort of patients with a MPD were examined.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myeloproliferative disorders

Fourouclas¹,

Li²,

Gilby³

et al. 2008

Haematologica

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myeloproliferative disorders

Fourouclas¹,

Li²,

Gilby³

et al. 2008

Haematologica

View full text Add to dashboard Cite

show abstract

“…Indeed, SOCS6 is strongly downregulated in the most-severe cases of prostate cancer (136), hepatocellular carcinoma (137), lung cancer (138), and gastric cancer (139). SOCS3 is downregulated in head and neck cancer (140) and Barrett's adenocarcinoma (141). High expression of SOCS4 and -7 is associated with improved clinical outcome in breast cancer (142), loss of SOCS5 correlates with poor outcome in liver cancer (143), and decreased SOCS2 expression correlates with shorter recurrence-free survival in prostate cancer (136).…”

Section: Cell Regulation By Crl5: Studies With Cul5 and Rbx2mentioning

confidence: 99%

Cell Regulation by Phosphotyrosine-Targeted Ubiquitin Ligases

Cooper

Kaneko

2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

Three classes of E3 ubiquitin ligases, members of the Cbl, Hakai, and SOCS-Cul5-RING ligase families, stimulate the ubiquitination of phosphotyrosine-containing proteins, including receptor and nonreceptor tyrosine kinases and their phosphorylated substrates. Because ubiquitination frequently routes proteins for degradation by the lysosome or proteasome, these E3 ligases are able to potently inhibit tyrosine kinase signaling. Their loss or mutational inactivation can contribute to cancer, autoimmunity, or endocrine disorders, such as diabetes. However, these ligases also have biological functions that are independent of their ubiquitination activity. Here we review relevant literature and then focus on more-recent developments in understanding the structures, substrates, and pathways through which the phosphotyrosine-specific ubiquitin ligases regulate diverse aspects of cell biology. Phosphorylation and ubiquitination are among the commonest and best-studied posttranslational modifications of proteins. A phosphate group or ubiquitin molecule can trigger or obstruct protein-protein interactions, alter subcellular localization, stabilize a particular protein conformation, or have myriad other effects. Phosphorylation is directly catalyzed by protein kinases, but ubiquitination is more complex, requiring sequential activity of E1, E2, and E3 ubiquitin-activating, -conjugating, and -ligating enzymes (1-5). E3 ubiquitin ligases fall into two major groups: HECT domain ligases receive ubiquitin from an E2 enzyme and transfer it to a bound substrate, while RING-type ligases position an E2-ubiquitin conjugate near a substrate protein to facilitate ubiquitin transfer. Both phosphorylation and ubiquitination are reversible; protein phosphorylation is reversed by protein phosphatases and ubiquitination by deubiquitinating enzymes (DUBs) (6-8). Therefore, both phosphorylation/dephosphorylation and ubiquitination/deubiquitination can allow repeated cycles of protein modification. Reversible ubiquitination is particularly important in DNA repair and NF-B signaling. However, many ubiquitination events lead irreversibly to protein destruction, allowing regulation of protein turnover. For example, K48 polyubiquitin chains primarily route cytosolic proteins to the proteasome, while modification of many Lys residues with single ubiquitin molecules (multimonoubiquitination) has several functions, including routing membrane proteins for destruction in the lysosome (9-11). The irreversibility of proteolysis means that the ubiquitin-proteasome and ubiquitin-lysosome pathways directly control protein life spans.Protein phosphorylation and ubiquitination cross talk at many levels (12). In this review, we focus on situations where phosphorylation of a substrate creates a binding site for an E3 ligase, rendering ubiquitination dependent on prior phosphorylation of that substrate (13). Such phosphorylation-dependent substrate selection has particular importance because it can layer negative feedback onto an otherwise reversible phosphoryla...

show abstract

“…Indeed, SOCS-3 has been reported to be a tumor suppressor in breast cancer cells (Barclay et al, 2009), and methylation of CpG islands within the SOCS-3 promoter regions occurs frequently in a variety of cancers, including melanoma (Tokita et al, 2007), glioblastoma (Martini et al, 2008), head and neck squamous cell carcinoma (Weber et al, 2005), and cancers of the lung (He et al, 2003b) and gut (Tischoff et al, 2007), thereby preventing SOCS-3 induction and limiting its damping actions on cell growth. Despite this, inhibition of SOCS-3 induction in macrophages may actually be therapeutic for the suppression of tumor metastasis, because hyperactivation of STAT3 in these cells simultaneously exerts anti-inflammatory as well as antitumor effects through the concomitant suppression of IL-6 and TNF␣ production and increased production of monocyte chemotactic protein 2 (Hiwatashi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase-Dependent SOCS-3 Gene Induction Requires c-Jun, Signal Transducer and Activator of Transcription 3, and Specificity Protein 3 Transcription Factors

Wiejak¹,

Dunlop²,

Gao³

et al. 2012

Mol Pharmacol

View full text Add to dashboard Cite

SOCS-3 gene induction by cAMP-elevating agents or the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), in primary HUVECs was found to require PKC-and PKC-dependent extracellular signal-regulated kinase (ERK) activation. The minimal, ERK-responsive element of the SOCS-3 promoter was localized to a region spanning nucleotides Ϫ107 to the transcription start site and contains conserved binding sites for AP-1 and SP1/SP3 transcription factors, as well as proximal and distal signal transducer and activator of transcription (pSTAT and dSTAT) binding elements. All three classes of transcription factor were activated in response to ERK activation. Moreover, representative protein components of each of these transcription factor binding sites, namely c-Jun, STAT3, and SP3, were found to undergo ERKdependent phosphorylation within their respective transactivation domains. Mutational analysis demonstrated an absolute requirement for the SP1/SP3 binding element in controlling basal transcriptional activity of the minimal SOCS-3 promoter. In addition AP-1, pSTAT, and SP1/SP3 binding sites were required for ERK-dependent, PMA-stimulated SOCS-3 gene activation. The dSTAT site seems to be important for supporting activity of the AP-1 site, because combined deletion of both sites completely blocks transcriptional activation of SOCS-3 by PMA. Together these results describe novel, ERK-dependent regulation of transcriptional activity that requires codependent activation of multiple transcription factors within the same region of the SOCS-3 gene promoter.

show abstract

Methylation of SOCS-3 and SOCS-1 in the carcinogenesis of Barrett's adenocarcinoma

Cited by 83 publications

References 33 publications

Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myeloproliferative disorders

Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myeloproliferative disorders

Cell Regulation by Phosphotyrosine-Targeted Ubiquitin Ligases

Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase-Dependent SOCS-3 Gene Induction Requires c-Jun, Signal Transducer and Activator of Transcription 3, and Specificity Protein 3 Transcription Factors

Contact Info

Product

Resources

About