1 Introduction</h5> STAT3 is a transcription factor that participates in critical cellular processes involving cell-cycle progression and the anti-apoptotic program  . STAT3 is activated by tyrosine and serine phosphorylation in response to IL-6 type of cytokines and growth factors, leading to the formation of dimers that rapidly translocate into the nucleus and activate the promoters of target genes [2,3] . Aberrant constitutive STAT3 activation is frequently found in various types of cancer [4,5] and in autoimmune and inflammatory disorders, where it plays a deleterious role through prolonged activation of BCL2L1 , BCL2 , MYC and CCND1 , target genes  . STAT3 has been also classified as an oncogene because of its predominant role in mediating cellular transformation by v-src and in promoting tumor progression in nude mice [7,8] .</P>The regulation of STAT3 transcriptional activity mainly depends on posttranslational modifications (PTMs); these PTMS trigger STAT3 dimerization, nuclear translocation, complex formation with nuclear coactivators and/or its degradation. Although phosphorylation is the hallmark of STAT3 transcriptional activity [9–11] (tyrosine 705 and serine 727 phosphorylations are required for STAT3 dimerization and maximal transactivation, respectively), several other PTMs are also known to tightly regulate STAT3 function. For instance, the recently reported
Cellular Signalling – Elsevier
Published: Jul 1, 2014
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