HSF4 regulates lens fiber cell differentiation by activating p53 and its downstream regulators

摘要: Cataract refers to opacities of the lens that impede passage light. Mutations in heat shock transcription factor 4 (HSF4) have been associated with cataract; however, mechanisms regarding how mutations HSF4 cause cataract are still obscure. In this study, we generated an hsf4 knockout zebrafish model using TALEN technology. The mutant developed early-onset multiple developmental defects lens. epithelial cells were overproliferated, resulting overabundance fiber hsf4null Consequently, arrangement became more disordered and irregular age. More importantly, terminal differentiation cell was interrupted as organelles cannot be cleaved due time. cultured human cells, could stabilize retain p53 nucleus activate its target genes such fas surface death receptor (Fas) Bcl-2-associated X apoptosis regulator (Bax). fish, both activated-caspase3 significantly decreased. Combined finding denucleation defect partially rescued through microinjection p53, bax mRNA into embryos, directly proved promotes by activating downstream regulators. data presented suggest apoptosis-related involved differentiation. Our functions upstream these highlighted new regulatory modes cell.