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您的检索式：作者名="Xiaming Pang"
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| 1 | BH3-only proteins target BCL-xL/MCL-1,not BAX/BAK,to initiate apoptosis显示文摘It has been widely accepted that mitochondria-dependent apoptosis initiates when select BH3-only proteins(BID,BIM,etc.)directly engage and allosterically activate effector proteins BAX/BAK.Here,through reconstitution of cells lacking all eight pro-apoptotic BH3-only proteins,we demonstrate that all BH3-only proteins primarily target the anti-apoptotic BCL-2 proteins BCL-xL/MCL-1,whose simultaneous suppression enables membrane-mediated spontaneous activation of BAX/BAK.BH3-only proteins*apoptotic activities correlate with affinities for BCL-xL/MCL1 instead of abilities to directly activate BAX/BAK.Further,BID and BIM do not distinguish BAX from BAK or accelerate BAX/BAK activation following inactivation of BCL-xL/MCL-1.Remarkably,death ligandinduced apoptosis in cells lacking BH3-only proteins and MCL-1 is fully restored by BID mutants capable of neutralizing BCL-xL,but not direct activation of BAX/BAK.Taken together,our findings provide a'Membrane-mediated Permissive'model,in which the BH3-only proteins only indirectly activate BAX/BAK by neutralizing the anti-apoptotic BCL-2 proteins,and thus allowing BAX/BAK to undergo unimpeded,spontaneous activation in the mitochondrial outer membrane milieu,leading to apoptosis initiation. | Kai Huang Katelyn L.O'Neill Jian Li Wei Zhou Na Han Xiaming Pang Wei Wu Lucas Struble Gloria Borgstahl Zhaorui Liu Liqiana Zhang Xu Luo | 2019 | Cell Research2019，29，11： | 16 |
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