title: Akt phosphorylates acinus and inhibits its proteolytic cleavage, preventing chromatin condensation.
abstract: Akt promotes cell survival by phosphorylating and inhibiting components of the intrinsic cell death machinery. Akt translocates into the nucleus upon exposure of cells to survival factors, but little is known about its functions in the nucleus. Here, we show that acinus, a nuclear factor required for apoptotic chromatin condensation, is a direct target of Akt. We demonstrate that Akt phosphorylation of acinus on serine 422 and 573 results in its resistance to caspase cleavage in the nucleus and the inhibition of acinus-dependent chromatin condensation. Abolishing acinus phosphorylation by Akt through mutagenesis accelerates its proteolytic degradation and chromatin condensation. Acinus S422, 573D, a mutant mimicking phosphorylation, resists against apoptotic cleavage and prevents chromatin condensation. Knocking down of acinus substantially decreases chromatin condensation, and depletion of Akt provokes the apoptotic cleavage of acinus. Thus, Akt inhibits chromatin condensation during apoptosis by phosphorylating acinus in the nucleus, revealing a specific mechanism by which nuclear Akt promotes cell survival.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Hu
authors.forename: Joyce
authors.initials: J
authors.lastname: Yao
authors.forename: Zhixue
authors.initials: Z
authors.lastname: Liu
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Haian
authors.initials: H
authors.lastname: Fu
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D053938:DNA Fragmentation; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats
chemical_list: C121310:ACIN1 protein, human; D002843:Chromatin; D009687:Nuclear Proteins; D051057:Proto-Oncogene Proteins c-akt