CKIP-1 recruits nuclear ATM partially to the plasma membrane through interaction with ATM.
CKIP-1 (casein kinase-2 interacting protein-1) is implicated in muscle differentiation, regulation of cell morphology and actin cytoskeleton. More recently, we showed that CKIP-1 regulated AP-1 activity and promoted apoptosis via caspase-3-dependent cleavage and translocation. Here, we report that overexpression of CKIP-1 in SK-BR-3 breast cancer cells prevents p53 degradation induced by cycloheximide treatment through increase of p53 N-terminal Ser-15 phosphorylation level. CKIP-1 could interact with ATM, which is an upstream kinase of p53, thereby enhance the stability of p53. Interestingly, CKIP-1 is localized both at the plasma membrane and in the nucleus dependent on the cell types, and only the plasma membrane-localized CKIP-1 could form a complex with ATM. Importantly, CKIP-1 recruits nuclear ATM proteins partially to the plasma membrane. Our data provide the first evidence that ATM, a predominantly nuclear kinase, could be relocalized to the plasma membrane by CKIP-1 and shed new light on the multi-functional CKIP-1.
Zhang
Lingqiang
L
Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing Proteome Reseacrh Center, Beijing 100850, P.R. China. zhanglq@nic.bmi.ac.cn
Tie
Yi
Y
Tian
Chunyan
C
Xing
Guichun
G
Song
Yi
Y
Zhu
Yunping
Y
Sun
Zhixian
Z
He
Fuchu
F
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003513:Cycloheximide / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C408877:PLEKHO1 protein, human; D011500:Protein Synthesis Inhibitors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D003513:Cycloheximide; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases