title: CDK7 regulates the mitochondrial localization of a tail-anchored proapoptotic protein, Hid.
abstract: The mitochondrial outer membrane is a major site of apoptosis regulation across phyla. Human and C. elegans Bcl-2 family proteins and Drosophila Hid require the C-terminal tail-anchored (TA) sequence in order to insert into the mitochondrial membrane, but it remains unclear whether cytosolic proteins actively regulate the mitochondrial localization of these proteins. Here, we report that the cdk7 complex regulates the mitochondrial localization of Hid and its ability to induce apoptosis. We identified cdk7 through an in vivo RNAi screen of genes required for cell death. Although CDK7 is best known for its role in transcription and cell-cycle progression, a hypomorphic cdk7 mutant suppressed apoptosis without impairing these other known functions. In this cdk7 mutant background, Hid failed to localize to the mitochondria and failed to bind to recombinant inhibitors of apoptosis (IAPs). These findings indicate that apoptosis is promoted by a newly identified function of CDK7, which couples the mitochondrial localization and IAP binding of Hid.
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Morishita
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Fidelin
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: hyungdon.ryoo@nyumc.org.
authors.forename: Hyung Don
authors.initials: HD
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D017209:Apoptosis; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D009479:Neuropeptides; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase