p53 REEPs to sow ER-mitochondrial contacts
The intrinsic pathway of apoptosis requires mitochondrial outer membrane permeabilization,a process that can be facilitated by mitochondrial Ca2+ influx.In a recent paper published in Cell Research,Zheng and colleagues now show that p53-mediated changes in ER morphology,specifically in response to DNA damage,contribute to the induction of apoptosis.The tumor suppressor p53 is a master regulator of cell fate determination in response to DNA damage.1 As a transcription factor,p53 induces the upregulation of thousands of transcripts,which have various roles in the cellular response to the sustained damage.A fatal outcome of genotoxic stress is apoptosis,the controlled destruction of the cell if the damage is too severe.p53 is directly responsible for the transcription of a number of genes essential in this process,most importantly the BH3-only protein Puma.2,3 It can inactivate the pro-survival members of the Bcl-2 family of proteins,which then leads to activation of the proapoptotic proteins BAX and BAK.They are capable of promoting mitochondrial outer membrane permeabilization (MOMP),which subsequently leads to the release of soluble mitochondrial intermembrane space proteins (most importantly cytochrome c).4 These proteins can then activate proteolytic caspases,which cleave specific target proteins and therefore execute apoptosis.
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2018-10-22（万方平台首次上网日期，不代表论文的发表时间）
共2页
877-878
