TIS21/BTG2/PC3 accelerates the repair of DNA double strand breaks by enhancing Mre11 methylation and blocking damage signal transfer to the Chk2T68–p53S20 pathway

Effects of Low Doses of Ionizing Radiation Exposures on Stress-Responsive Gene Expression in Human Embryonic Stem Cells

“…BTG2 is a known tumor suppressor preventing cell proliferation; it is transiently induced by oxidative stress through both TP53 and NF-κB pathways [72], stimulating repair of DNA double-strand breaks (DSBs) [73] and cellular antioxidant defenses [74]. Our results indicate that the modulations in BTG2 expression following LD of IR exposures are highly temporal- and cell line-dependent in hESCs (Figure 4).…”

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

“…The data accumulated during the past two decades with both cells and animal models implicate Btg2/TIS21/PC3 (Btg2) in a variety of biological processes such as mediation of stage specific expansion of developing thymocytes [13], regulation of the hematopoietic progenitor cell expansion in response to estradiol [14], cell cycle arrest at G2/M [15] and G1/S phases [16,17], enhancement of cancer cell death via interaction with Pin-1 in response to growth factor stimulation [18] or via accumulation of hydrogen peroxide after doxorubicin treatment [19], and regulation of neuronal differentiation [20,21]. Moreover, Btg2 is involved in the differentiation of myelocytic leukemia cells and CD34 + hematopoietic precursor cells [22,23], DNA repair [24,25], inhibition of cancer cell migration [26], as a transcriptional co-regulator in different model systems, and in the antioxidant defenses through the antioxidant transcription factor NFE2L2 [22,27].…”

Protein Methylation and Interaction with the Antiproliferative Gene, BTG2/TIS21/Pc3

“…The physiological functions of the MRE11/Rad50/NBS1 complex and their interactions with other molecules might explain the wide clinical presentation observed in patients with chromosome instability syndrome. We previously reported regulations of Mre11 and PRMT1 activity by BTG2 using TIS21KO mouse embryonic fibroblasts and adenoviral transduction of the TIS21 gene into Huh7 cancer cells 83. Expression of BTG2 increased methylation of Mre11 and PRMT1 activity, leading to1 Mre11 activation in vitro and in vivo .…”

“…Data accumulated during the past two decades with both cells and animal models implicate that BTG2 /TIS21/PC3 (BTG2) plays roles in various biological processes such as mediation of stage specific expansion of developing thymocytes,71 regulation of the hematopoietic progenitor cell expansion in response to estradiol,72 cell cycle arrest at G2/M73 and G1/S phases,74,75 enhancement of cancer cell death via interaction with Pin-1 in response to growth factor stimulation76 or via accumulation of hydrogen peroxide after doxorubicin treatment,77 and regulation of neuronal differentiation 78,79. Moreover, BTG2 is involved in the differentiation of myelocytic leukemia cells and CD34 + hematopoietic precursor cells,80,81 DNA repair,82,83 inhibition of cancer cell migration84 as a transcriptional co-regulator in different model systems, and in the antioxidant defenses through the antioxidant transcription factor NFE2L2 80,85. Murine BTG2 gene, TIS21, has originally been identified as a primary response gene86 induced by stimulations with either growth factors, tumor promoters, a high concentration of serum addition, Ca ++ flux changes, or depolarization.…”

“…In 1996, Herschman's group cloned protein methyltransferase, which interacts with mammalian immediate-early gene, TIS21 /BTG2/Pc3 and leukemia-associated B-cell translocation gene (BTG1), through the yeast two hybrid system and renamed it as PRMT (protein-arginine N-methyltransferase),88 which corresponds to our protein methylase I. PRMT1 was found to be bound to Box C domain of BTG1 and BTG2,89 and the interaction of PRMT1 with BTG2 significantly increased the activity of PRMT1,83 strongly suggesting BTG2 as a regulating factor of PRMTs. Meanwhile, we observed the in vitro methylation of recombinant TIS21 /BTG2/Pc3 protein by protein methylase I,90 indicating TIS21 is one of the PRMT substrates.…”