title: Steroid receptor coactivator-interacting protein (SIP) inhibits caspase-independent apoptosis by preventing apoptosis-inducing factor (AIF) from being released from mitochondria.
abstract: Apoptosis-inducing factor (AIF) is a caspase-independent death effector. Normally residing in the mitochondrial intermembrane space, AIF is released and translocated to the nucleus in response to proapoptotic stimuli. Nuclear AIF binds to DNA and induces chromatin condensation and DNA fragmentation, characteristics of apoptosis. Until now, it remained to be clarified how the mitochondrial-nuclear translocation of AIF is regulated. Here we report that steroid receptor coactivator-interacting protein (SIP) interacts directly with AIF in mitochondria and specifically inhibits caspase-independent and AIF-dependent apoptosis. Challenging cells with apoptotic stimuli leads to rapid degradation of SIP, and subsequently AIF is liberated from mitochondria and translocated to the nucleus to induce apoptosis. Together, our data demonstrate that SIP is a novel regulator in caspase-independent and AIF-mediated apoptosis.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Gui
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Yi
authors.forename: Luyang
authors.initials: L
authors.lastname: Sun
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism*
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D049452:Green Fluorescent Proteins; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D020169:Caspases