Article
- The EMBO Journal (2005) 24, 766 - 778
- doi:10.1038/sj.emboj.7600532
Published online: 10 February 2005
Subject Categories:
Role for the pleckstrin homology domain-containing protein CKIP-1 in AP-1 regulation and apoptosis
Lingqiang Zhang1, Guichun Xing1, Yi Tie2, Ying Tang1, Chunyan Tian1, Li Li1, Libo Sun1, Handong Wei1, Yunping Zhu1 and Fuchu He1,3
- Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Chinese Human Genome Center of Beijing, Beijing, PR China
- Department of Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Chinese Human Genome Center of Beijing, Beijing, PR China
- Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China
Correspondence to:
Fuchu He, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, PR China. Tel./Fax: +86 10 681 712 08; E-mail: hefc@nic.bmi.ac.cn
Received 28 June 2004; Accepted 3 December 2004
Abstract
The oncogenic transcription factor c-Jun plays an important role in cell proliferation, transformation and differentiation. All identified c-Jun-interacting proteins are localized to the nucleus or cytoplasm and function in their intact forms. Here we show that the pleckstrin homology domain-containing protein CKIP-1 (casein kinase 2-interacting protein-1) functions as a plasma membrane-bound AP-1 regulator. During apoptosis, CKIP-1 is cleaved by caspase-3 and translocated to the cytoplasm and then to the nucleus. C-terminal fragments of cleaved CKIP-1 strongly repress AP-1 activity. Importantly, CKIP-1 overexpression promotes apoptosis by forming a positive feedback loop between CKIP-1 and caspase-3. RNA interference of CKIP-1 or overexpression of c-Jun attenuates the sensitivity to apoptosis, indicating a novel role of CKIP-1 in apoptosis. CKIP-1 is the first case of a c-Jun-interacting protein that regulates AP-1 activity via caspase-3-dependent cleavage and translocation.
Keywords:
- AP-1,
- apoptosis,
- caspase-3,
- CKIP-1
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