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 On top of that, there's a region upstream which acts as an  Empty On top of that, there's a region upstream which acts as an

Post  jy9202 on Sun Feb 15, 2015 7:25 am

Discussion The result of PKC activators PMA and Bryostatin one on IFNg inducibility of MHCII in three resistant tumor cell lines of various histological origin is examined. We observed that PKC activators rescued large levels of MHCII expres sion in colon carcinoma cells and failed to accomplish [You must be registered and logged in to see this link.] so in mes othelioma and hepatocellular carcinoma cells. A bad response of tumor cells to IFNg is in agreement with pre vious observations that lots of tumors acquire this kind of resist ance on malignant transformation, probably important like a mechanism of tumor escape from immune surveillance. The nature of this phenomenon is com plex, and numerous defects that can reduce IFNg responses in tumor lines have been described.

Most regularly, bad MHCII inducibility in response to IFNg has been attributed to alterations during the IFNg [You must be registered and logged in to see this link.] signalling pathway and epigenetic silencing of gene ex pression. The cascade of IFNg sig nalling events leading to transcription activation of MHCII genes has become characterized in great detail. Binding of IFNg to its receptor ends in JAK mediated phosphorylation of STAT1 on Tyrosine 701. Moreover, IFNg interaction with the receptor leads to p38MAPK mediated phosphorylation of STAT1 on Ser ine 727. The phosphorylated STAT1 dimerizes and translocates in to the nucleus wherever it activates transcrip tion of numerous other aspects which includes CIITA. Al however the outcomes of this review do not enable us to describe the precise mechanism of PMA involvement in IFNg signal ling in LS1034 cell, at the least two non mutually unique situations might be hypothesized 1.

[You must be registered and logged in to see this link.] PMA could act through the JAK STAT signalling path way. It has been established that, to achieve its maximal transcriptional activity, STAT1 must be phosphorylated on the two Tyr701 and Ser727. Phosphorylation of STAT1 on Ser727 occurs in response to LPS, UV irradia tion together with other agents that activate the p38MAPK pathway. As phorbol esters can also stimulate the MAPK cas cade by activation of PKC, it is tempting to speculate that combined treatment method of cells with PMA and IFNg could increase the pool of STAT1 molecules phos phorylated on each Tyr701 and Ser727. This impact is more than likely mediated by PKC delta isoenzyme as this particular PKC isoform seems to get significant for phosphorylation of STAT1 on Ser727 and activation of p38MAPK. two.

Alternatively, PMA therapy could initiate a cascade of protein phosphorylation leading to the improve in tran scriptional activity of chromatin at the type IV promoter of CIITA and/or promoter of MHCII genes. Expression of many genes could be modified by therapy with agents act ing with the amount of enzymes and nuclear receptors that modify transcriptional activity of chromatin. Consequently, his tone deacetylase inhibitors Butyrate and Trichostatin A can rescue MHCII inducibility in bladder carcinoma cells and restore constitutive MHCII expression in plasmacytoma cells. On top of that to acetylation, tran scriptional action of chromatin can be regulated as a result of phosphorylation. It's been proven that remedy of cells with phorbol esters leads to accumulation of phosphorylated H3 histones.


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