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Updated: Aug 12, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
CKIP-1 recruits nuclear ATM partially to the plasma membrane through interaction with ATM
Lingqiang Zhang1, Yi Tie, Chunyan Tian
1Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing Proteome Reseacrh Center, Beijing 100850, P.R. China. zhanglq@nic.bmi.ac.cn
Abstract:
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.
Insights
Casein kinase-2 interacting protein-1 (CKIP-1) stabilizes the tumor suppressor p53 by interacting with ATM kinase. CKIP-1 also relocates ATM to the plasma membrane, revealing new functions for CKIP-1.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Casein kinase-2 interacting protein-1 (CKIP-1) is involved in muscle differentiation and cytoskeleton regulation.
- Previous studies demonstrated CKIP-1's role in regulating AP-1 activity and promoting apoptosis.
- CKIP-1's interaction with ATM kinase and its effect on p53 stability are not fully understood.
Purpose of the Study:
- To investigate the role of CKIP-1 in p53 degradation and stability in breast cancer cells.
- To explore the interaction between CKIP-1 and ATM kinase.
- To elucidate the subcellular localization of CKIP-1 and its impact on ATM localization.
Main Methods:
- Overexpression of CKIP-1 in SK-BR-3 breast cancer cells.
- Cycloheximide treatment to induce p53 degradation.
- Western blotting to assess p53 levels and phosphorylation.
- Co-immunoprecipitation to detect protein interactions.
- Immunofluorescence microscopy to determine protein localization.
Main Results:
- CKIP-1 overexpression prevented p53 degradation induced by cycloheximide.
- CKIP-1 increased p53 N-terminal Ser-15 phosphorylation, enhancing p53 stability.
- CKIP-1 interacted with ATM kinase, an upstream kinase of p53.
- CKIP-1 localized to both plasma membrane and nucleus, with plasma membrane-localized CKIP-1 forming a complex with ATM.
- CKIP-1 recruited nuclear ATM to the plasma membrane.
Conclusions:
- CKIP-1 enhances p53 stability by increasing its phosphorylation and preventing degradation.
- CKIP-1 interacts with ATM kinase and influences its subcellular localization.
- CKIP-1's ability to relocate ATM to the plasma membrane highlights its multifaceted roles in cellular processes.
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