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  • The EMBO Journal (2005) 24, 3543 - 3554
  • doi:10.1038/sj.emboj.7600823

Published online: 22 September 2005

Akt phosphorylates acinus and inhibits its proteolytic cleavage, preventing chromatin condensation

Yuanxin Hu1,2, Joyce Yao1,2, Zhixue Liu1,2, Xia Liu1,2, Haian Fu2 and Keqiang Ye1

  1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
  2. Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, USA

Correspondence to:

Keqiang Ye, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Room 145, Whitehead Building, 615 Michael Street, Atlanta, GA 30322, USA. Tel.: +1 404 712 2814; Fax: +1 404 712 2979; E-mail: kye@emory.edu

Received 24 January 2005; Accepted 30 August 2005

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.

  • Keywords:

    • acinus,
    • Akt,
    • chromatin condensation,
    • phosphorylation