*3.1. Transcriptional Regulation*

To date, numerous instances of transcriptional regulation of TCTP synthesis have been reported [5], but precise mechanistic investigations were only performed in a few cases. Thiele and coworkers demonstrated that TCTP synthesis is induced by phorbolester (PMA) through the cAMP-PKA signalling pathway and activation of transcription factor CREB [58]. They also studied the regulation of TCTP expression under stress conditions, such as heavy metals, and showed that copper induced TCTP synthesis at both the transcriptional and the translational level [59]. Several similar studies showed that TCTP is transcriptionally regulated under a variety of stress conditions [5].

Of particular relevance for cancer research was the demonstration that the tumor suppressor protein p53, acting as a transcription factor, negatively a ffects TCTP expression [40]. Since p53 is frequently mutated in cancers, this contributes to the observed deregulation of TCTP synthesis in cancers. A more recent paper reported another example of transcriptional regulation of TCTP expression [31]. The authors studied a specific transcription factor, insulin-response element binding protein 1 (IRE-BP1), whose decreased expression in insulin target tissues contributes to the development of insulin-resistant diabetes in rats. Normally, insulin-induced PI3K signalling results in the proteolytic cleavage of IRE-BP1 and release of the active C-terminal fragment of the protein. In order to study the target genes of IRE-BP1, the investigators analysed the proteome of pancreatic islets from transgenic mice overexpressing the active fragment of IRE-BP1, compared to the corresponding proteome from control mice. The overexpression of two of the identified target genes of IRE-BP1 in the transgenic mice was further confirmed by Western blotting, specifically the genes for RACK1 and for TCTP. Moreover, the authors discovered the interaction of RACK1 with TCTP by Co-IP experiments [31].
