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CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced signaling by targeting ASK1

Kyoung Wan Yoon1, Jun-Ho Cho, Jae Keun Lee

  • 1Laboratories of Cell Death and Human Diseases, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.

Proceedings of the National Academy of Sciences of the United States of America
|October 7, 2009
PubMed

Insights

Calcium and integrin binding protein 1 (CIB1) acts as a Ca(2+)-sensitive regulator, inhibiting stress-activated MAPK pathways by targeting apoptosis signal-regulating kinase 1 (ASK1) and preventing cell death.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Calcium and integrin binding protein 1 (CIB1) is a Ca(2+)-binding protein involved in various cellular functions.
  • The precise molecular mechanisms by which CIB1 regulates intracellular signaling remain unclear.

Purpose of the Study:

  • To elucidate the role of CIB1 in regulating stress-activated MAPK signaling pathways.
  • To investigate how CIB1 interacts with and modulates apoptosis signal-regulating kinase 1 (ASK1).

Main Methods:

  • Investigated CIB1-ASK1 interaction using biochemical assays.
  • Assessed the effect of CIB1 on ASK1 activation and autophosphorylation at threonine-838.
  • Evaluated CIB1's impact on TNF-alpha and 6-hydroxydopamine (6-OHDA) induced apoptosis in relevant cell lines.

Main Results:

  • CIB1 directly binds to ASK1, inhibiting its activation by blocking TRAF2 recruitment and ASK1 autophosphorylation.
  • CIB1 significantly mitigates apoptotic cell death induced by TNF-alpha in breast cancer cells and 6-OHDA in dopaminergic cells.
  • Calcium influx reverses CIB1's inhibitory effects on ASK1 activation and cell death in dopaminergic neurons.

Conclusions:

  • CIB1 functions as a Ca(2+)-sensitive negative regulator of ASK1-mediated stress signaling.
  • CIB1 plays a critical role in controlling apoptosis through the ASK1 pathway.
  • These findings reveal a novel mechanism of CIB1 in cellular stress response and survival.

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