Premium
Role for the pleckstrin homology domain‐containing protein CKIP‐1 in AP‐1 regulation and apoptosis
Author(s) -
Zhang Lingqiang,
Xing Guichun,
Tie Yi,
Tang Ying,
Tian Chunyan,
Li Li,
Sun Libo,
Wei Handong,
Zhu Yunping,
He Fuchu
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600532
Subject(s) - pleckstrin homology domain , biology , homology (biology) , apoptosis , microbiology and biotechnology , protein domain , genetics , signal transduction , gene
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.