TBX3 and its splice variant TBX3 + exon 2a are functionally similar

摘要: Tbx3, a member of the conserved family T-box developmental transcription factors, is transcriptional repressor required during cardiogenesis for formation and specification sinoatrial node, pacemaker heart. Both TBX3 highly related TBX2 genes are also associated with several cancers, most likely as consequence their powerful anti-senescence properties mediated via suppression p14(Arf) p21(CIP) expression. In melanoma, gene frequently amplified inhibition Tbx2 function leads to senescence up-regulation p21(CIP), target gene. Tbx3 + 2a splice variant containing an extra 20 amino acids encoded by exon inserted into DNA-binding domain. We find here that evolutionary similar insertions largely absent from domains other factors. has been reported lack ability act functional antagonist Tbx3. By contrast, we now demonstrate both bind consensus T-element, p21(CIP1) promoter, Nppa cardiac isoforms repressors promoter activity interact homeobox factor Nkx2-5. When ectopically expressed in embryonic heart mice, suppressed chamber repressed expression markers Cx40. The results suggest assays used, functionally equivalent like Tbx2, may melanoma.