Role for the pleckstrin homology domain-containing protein CKIP-1 in AP-1 regulation and apoptosis.
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.
Zhang
Lingqiang
L
Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Chinese Human Genome Center of Beijing, Beijing, PR China.
Xing
Guichun
G
Tie
Yi
Y
Tang
Ying
Y
Tian
Chunyan
C
Li
Li
L
Sun
Libo
L
Wei
Handong
H
Zhu
Yunping
Y
He
Fuchu
F
D000818:Animals; D017209:Apoptosis; D001798:Blood Proteins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D010750:Phosphoproteins / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D017385:Sequence Homology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001798:Blood Proteins; D002352:Carrier Proteins; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C039077:platelet protein P47; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases