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

Cellular Signalling
|December 6, 2005
PubMed

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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