Novel Growth and Death Related Interferon-Stimulated Genes (ISGs) in Melanoma: Greater Potency of IFN-<i>β</i>Compared with IFN-<i>α</i>2

Leaman, Douglas W.; Chawla‐Sarkar, Mamta; Jacobs, Barbara; Vyas, Keyur; Sun, Yaping; Ozdemir, Aylin M.; Yi, Taolin; Williams, Bryan R.G.; Borden, Ernest C.

doi:10.1089/107999003772084860

Cited by 116 publications

(90 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IFN has been also described as an inducer of apoptosis. 41 Consequently, we tested whether the appearance of large colonies could be due to 64G12 neutralizing the apoptotic effect of IFN. Cells after contact with 64G12 were analyzed by Annexin-V staining and flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

et al. 2007

View full text Add to dashboard Cite

Type I interferon (IFN) is shown to control the reversible quiescence of a primitive human bone marrow mesenchymal stem cell (MSC) subpopulation. A 24 h pre-treatment of Stro1 þ / GlycoA-or CD45-/GlycoA-subpopulations with a monoclonal antibody (mAb) against the IFNAR1 chain of the human type I IFN receptor (64G12), or with a polyclonal anti-IFNa antibody, resulted in a marked increase in the number of very large colonies (CFU-F 43000 cells) obtained in the presence of low, but necessary, concentrations of bFGF. Over a 2-month culture period, this short activation promoted a faster and greater amplification of mesenchymal progenitors for adipocytes and osteoblasts. Activation correlated with inhibition of STAT1 and STAT2 phosphorylation and of STAT1 nuclear translocation. A non-neutralizing anti-IFNAR1 mAb was ineffective. We demonstrate that control and activated MSCs express ST3GAL3, a sialyltransferase necessary to produce the embryonic antigens SSEA-3 and -4. Interestingly, activated MSC progeny expressed SSEA-3 and -4 at a higher level than control cultures, but this was not correlated with a significant expression of other embryonic markers. As MSCs represent an essential tool in tissue regeneration, the use of 64G12, which rapidly recruits a higher number of primitive cells, might increase amplification safety for cell therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Biological effects of IFNs result from transcriptional regulation of a subset of genes, called IFN-stimulated genes (ISGs). Gene microarray studies have identified >300 induced ISGs in fibrosarcoma or in melanoma cells treated with IFNs (Der et al, 1998;Leaman et al, 2003). ISG products implicated as contributing to IFN-induced apoptosis include Apo2L/TRAIL, FasL, XAF1, protein kinase R, death-associated protein kinase, IRF1, RNaseL and 2-5 OA synthetase .…”

Section: Introductionmentioning

confidence: 99%

Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL

et al. 2007

View full text Add to dashboard Cite

Human melanoma cell lines, SK-MEL-3 and SK-MEL-28, despite induction of the proapoptotic cytokine, Apo2L/TRAIL, did not undergo apoptosis in response to interferons . Postulating that genes important for apoptosis induction by IFNs might be silenced by methylation, the DNA demethylating agent 5-aza-2 0 -deoxycytidine (5-AZAdC) was assessed. DR4 (TRAIL-R1) was identified as one of the genes reactivated by 5-AZAdC with a >3-fold increase in 8 of 10 melanoma cell lines. Pretreatment with 5-AZAdC sensitized SK-MEL-3 and SK-MEL-28 cells to apoptosis induced by IFN-a2b and IFN-b; methylation-specific PCR and bisulfite sequencing confirmed demethylation of 5 0 CpG islands of DR4 and flow cytometry showed an increase in DR4 protein on the cell surface. In cells with reactivated DR4, neutralizing mAB to TRAIL reduced apoptosis in response to IFN-b or Apo2L/TRAIL. To further confirm the role of DR4, it was expressed by retroviral vector in SK-MEL-3 and SK-MEL-28 cells with reversal of resistance to IFN-b and Apo2L/TRAIL. Thus, reexpressing DR4 by 5-AZAdC or retroviral transfection in melanoma cell in which promoter methylation had suppressed its expression, potentiated apoptosis by IFNa2b, IFN-b and Apo2L/TRAIL. Reactivation of silenced proapoptotic genes by inhibitors of DNA methylation may enhance clinical response to IFNs or Apo2L/TRAIL.

show abstract

“…Both TNFR1 and TNFR2 are capable of triggering apoptosis (1), but this process can be modulated by factors such as MAPK8 signaling, polyamines, and silencer of death domain protein (30,31). Similarly, type 1 IFN can cause programmed cell death (2, 32) and up-regulate genes that drive apoptosis (3,33,34), most likely as part of an antiviral response. However, type I IFNs are not, under most circumstances, cytotoxic and can act as survival factors (4).…”

Section: Discussionmentioning

confidence: 99%

“…A delicate balance is maintained between pathways that promote survival or death, and this balance can be affected by a number of cytokines, including members of the IL, IFN, and TNF families (1). The type 1 IFN in particular have the ability to promote (2,3) or prevent (4) cell death depending on the circumstances. Exposure of cells to stress induces compensatory activation of multiple intracellular signaling pathways, among which is the one controlled by p38 MAPK (MAPK14), also known as stress-activated protein kinase (5).…”

mentioning

confidence: 99%

A link between SIN1 (MAPKAP1) and poly(rC) binding protein 2 (PCBP2) in counteracting environmental stress

Ghosh¹,

Srivastava²,

Xu³

et al. 2008

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

View full text Add to dashboard Cite

When SIN1 (MAPKAP1) was used as the bait in a two-hybrid screen of a human bone marrow cDNA library, its most frequent partner was poly(rC) binding protein 2 (PCBP2/hnRNP-E2), which associates with the N-terminal domain of SIN1 and can be coimmunoprecipitated with SIN1 and the cytoplasmic domain of the IFN receptor IFNAR2 from HeLa cells. SIN1, but not PCBP2, also associates with the receptors that bind TNF␣. PCBP2 is known to bind pyrimidinerich repeats within the 3 UTR of mRNAs and has been implicated in control of RNA stability and translation and selective capindependent transcription. RNAi silencing of either SIN1 or PCBP2 renders cells sensitive to basal and stress-induced apoptosis. Stress in the form of TNF␣ and H2O2 treatments rapidly raises the cell content of SIN1 and PCBP2, an effect reversible by inhibiting MAPK14. A meta analysis of human microarray information with an algorithm that discerns similarities in gene-regulatory profiles shows that SIN1 and PCBP2 are generally coregulated with large numbers of genes implicated in both cell survival and death and in cellular stress responses, including RNA translation and processing. We predict that SIN1 is a scaffold protein that organizes antiapoptotic responses in stressed cells, whereas PCBP2, its binding partner, provides for the selective expression of cell survival factors through posttranslational events.apoptosis ͉ interferon ͉ stress kinase-interacting protein 1 ͉ yeast two-hybrid assay W hen faced with environmental stressors such as reactive oxygen species, inflammatory shock, or viral infection, cells may react by either boosting protective mechanisms or undergoing programmed cell death. A delicate balance is maintained between pathways that promote survival or death, and this balance can be affected by a number of cytokines, including members of the IL, IFN, and TNF families (1). The type 1 IFN in particular have the ability to promote (2, 3) or prevent (4) cell death depending on the circumstances. Exposure of cells to stress induces compensatory activation of multiple intracellular signaling pathways, among which is the one controlled by p38 MAPK (MAPK14), also known as stress-activated protein kinase (5).We previously used yeast two-hybrid genetic screens to identify stress kinase-interacting protein 1 (SIN1; MAPKAP1) as a factor that associates with the IFN receptor subunit IFNAR2 (6). Cells in which the SIN1 gene has been ablated or where gene expression had been knocked down by RNAi silencing are susceptible to stress (7,8). SIN1 is represented as a single gene in all metazoan species and fungi so far examined, is highly conserved in vertebrates, and is expressed in most, if not all, tissues of the mouse (6). Despite this ubiquity, it has until recently been poorly studied, and its mechanisms of action remain unclear. It was originally described as a gene product that modulated RAS function in Saccharomyces cerevisiae (9). Later, a yeast two-hybrid screen of a Schizosaccharomyces pombe cDNA library identified an apparent ortholog of t...

show abstract

Novel Growth and Death Related Interferon-Stimulated Genes (ISGs) in Melanoma: Greater Potency of IFN-βCompared with IFN-α2

Cited by 116 publications

References 59 publications

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL

A link between SIN1 (MAPKAP1) and poly(rC) binding protein 2 (PCBP2) in counteracting environmental stress

Contact Info

Product

Resources

About