BTG gene expression in the p53-dependent and -independent cellular response to DNA damage

Abstract

Exposure of mammalian cells to genotoxic agents evokes a complex cellular response. An ordered series of molecular events is necessary to sense DNA damage, transduce the signal, and ultimately delay the cell cycle or trigger apoptosis. Recently, we have shown that BTG2/TIS21 gene expression was induced in response to DNA damage through a p53-dependent pathway. This gene belongs to a newly identified family of structurally related genes whose other known human members are BTG1, BTG3, and Tob. To define the respective involvement of these four related genes in the cellular response to DNA damage, we studied their expression in human cell lines after a variety of genotoxic treatments. Our results demonstrated that were BTG1, BTG2/TIS21, and Tob genes the DNA damage--inducible genes. However, BTG2/TIS21 appeared to be the only p53-transcriptional target gene. We speculate that BTG proteins may play a coordinate role in a general transduction pathway that is induced in response to DNA damage. It has been previously described that recombinant BTG1 and BTG2/TIS21 can physically interact with PRMT1, an arginine methyl transferase, suggesting that BTG1 and BTG2/TIS21 induction may lead to posttranslational modifications of cellular proteins. In support of this hypothesis, we showed that the endogenous induction of BTG1 and BTG2 after genotoxic treatment was correlated with a modulation of protein methylation.

Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways

“…Regarding BTG2 induction, two pathways have been demonstrated to involve in, which are p53 dependent1011, or p53 independent PKC-δ pathway12. In this study, we demonstrated for the first time that cisplatin treatment induced BTG2 expression in both p53-wild LNCaP cells and p53-null PC-3 cells.…”

“…In terms of cancer cells, BTG2 acts as a tumor suppressor gene in a number of cancers and is activated mainly by p53 dependent pathway subsequent to DNA damage1011. The p53 independent BTG2 expression is also possible through the PKC-δ pathway in p53-null cancer cells12.…”

Regulation of Btg2/TIS21/PC3 expression via reactive oxygen species–protein kinase C–ΝFκΒ pathway under stress conditions

“…There are six p53-and one NFκB-regulatory elements located in the promoter of Btg2 gene [32]. Despite the fact that almost half of the human cancers are p53 mutant [53], the expression of Btg2 is regulated by both p53-dependent and -independent mechanisms [15,42]. Furthermore, our previous report [15] on the PKC-δ mediated Btg2 upregulation in p53 null U937 cells manifests an example of p53-independent Btg2 expression.…”

“…However, serum deprivation led to a decrease of SP1 expression and additionally mithramycin A treatment failed to regulate Btg2 expression in DLD-1 cells, indicating the NFκB-, but not SP1, mediated Btg2 transcription under serum deprivation. Oxidative burst often induces DNA damage and the signal upregulates Btg2 expression in both p53-dependent and -independent manners [42]. Therefore, to (Fig.…”

Iodine-131 treatment of thyroid cancer cells leads to suppression of cell proliferation followed by induction of cell apoptosis and cell cycle arrest by regulation of B-cell translocation gene 2-mediated JNK/NF-κB pathways

“…B-cell translocation gene 2 (BTG2) acts as a tumor suppressor gene for a number of cancers and it is stimulated by a p53-dependent pathway, which subsequently leads to the DNA damage. BTG2 gene belongs to an anti-proliferative family protein which has highly conserved domains of BTG-Box A (Y50–N71) and BTG-Box B (L97–E115) (11 –14). It has been reported that amongst the numerous molecules that are involved in diverse anti- or pro-apoptotic signaling pathways, NF-kB is one of the key factors controlling anti-apoptotic responses.…”