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  • The EMBO Journal (2006) 25, 2083 - 2095
  • doi:10.1038/sj.emboj.7601111

Published online: 27 April 2006

Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase

Jee-Yin Ahn1,a, Xia Liu1, Zhixue Liu1, Lorena Pereira1, Dongmei Cheng2, Junmin Peng2, Paul A Wade1, Anne W Hamburger3 and Keqiang Ye1

  1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
  2. Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA
  3. Greene Baum Cancer Center, Department of Pathology, University of Maryland, Baltimore, MD, USA

Correspondence to:

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

aPresent address: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-76, Korea

Received 3 January 2006; Accepted 3 April 2006

Akt promotes cell survival through phosphorylation. The physiological functions of cytoplasmic Akt have been well defined, but little is known about the nuclear counterpart. Employing a cell-free apoptotic assay and NGF-treated PC12 nuclear extracts, we purified Ebp1 as a factor, which contributes to inhibition of DNA fragmentation by CAD. Depletion of Ebp1 from nuclear extracts or knockdown of Ebp1 in PC12 cells abolishes the protective effects of nerve growth factor, whereas overexpression of Ebp1 prevents apoptosis. Ebp1 (S360A), which cannot be phosphorylated by PKC, barely binds Akt or inhibits DNA fragmentation, whereas Ebp1 S360D, which mimics phosphorylation, strongly binds Akt and suppresses apoptosis. Further, phosphorylated nuclear but not cytoplasmic Akt interacts with Ebp1 and enhances its antiapoptotic action independent of Akt kinase activity. Moreover, knocking down of Akt diminishes the antiapoptotic effect of Ebp1 in the nucleus. Thus, nuclear Akt might contribute to suppressing apoptosis through interaction with Ebp1.

  • Keywords:

    • nuclear Akt,
    • Ebp1,
    • PKC,
    • CAD,
    • DNA fragmentation