ATFalpha课件.pptVIP

Figure 7: ATF6a protects from ER stress in vivo Conclusion ATF6a can bind to ER stress element and regulates the expression of ER stress responsive genes, and this function is overlapped with other ER stress signal pathways IRE1a and PERK. ATF6a participates in regulation of ERAD pathways and apoptosis pathways especially, during chronic ER stress. ATF6a paricipates in regulation of precondition of ER stress. ATF6a is an essential factor for chronic ER stress by regulation of persistent eIf2a phosphorylation,and upregulation of CHOP and GADD34. Thank You * * * * * * * * Cell Stress Response 胡延忠 Stressful factors Extracellular stresses: Heat shock, heavy metal, pathogen infection, nutrient, Radiation ( UV, x-ray) et al. Intracellular stresses: proteotoxin, superoxide, cell proliferation, DNA impairment. et al. Three Fundamental Adaptive Responses Heat Shock Response: Hsf1, Hsp70 UPR: General inhibition of protein synthesis and reduction of ER loading Upregulation of Grp proteins apoptosis Autophage: Heat shock response The cells are adapted to the variety of stresses by up-regulating the expression of heat shock proteins, which can chaperon the misfolded proteins and protect cell homeostasis. Regulators: Hsf1, Hsf2, Hsf3 and Hsf4 Effectors: heat shock proteins Heat shock factors Hsf1: the dominant transcriptional factor of heat shock response(HSR). Being activated by variety of stresses. Hsf2: assistant regulation of Hsf1-mediated HSR. Being activated by MG132.Regulating the differentiation of Red blood cells Hsf3: being activated by heat shock, regulating the expression of heat-induced proteins without heat shock protein activity. Hsf4: constitutively active, is the key regulator of lens development. Heat shock protein family Heat shock proteins are known as molecular chaperons that can regulate protein folding, sorting and assemble. Heat shock protein family members: Hsp100 : Hsp110 and Hsp104 Hsp90 family: Hsp90a, Hsp90b and Grp94 Hsp70: Hsc70, Hsp70i,