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Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein

Longzhen Piao1, Yuwen Li, Keum-Jin Yang

  • 1Department of Pharmacology, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Taejeon, 301-131, Korea. plz1978@hanmail.net

BMC Cell Biology
|July 17, 2009
PubMed
Abstract

Insights

Phosphorylation of carboxyl-terminal modulator protein (CTMP) on Ser37/Ser38 regulates its mitochondrial localization, impacting cell death. CTMP plays a key role in mitochondria-mediated apoptosis and protein kinase B (PKB) inhibition.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The serine/threonine protein kinase B (PKB/Akt) pathway is crucial for insulin signaling, cell survival, and transformation.
  • Carboxyl-terminal modulator protein (CTMP) is a novel PKB binding partner and a potential tumor suppressor.
  • The role of CTMP in apoptosis requires further investigation.

Purpose of the Study:

  • To elucidate novel mechanisms by which CTMP influences apoptosis.
  • To investigate the role of CTMP phosphorylation in apoptosis.
  • To determine CTMP's subcellular localization and its impact on cell death.

Main Methods:

  • Yeast two-hybrid screening to identify PKB binding partners.
  • Cellular localization studies using microscopy.
  • In vivo phosphorylation analysis using pervanadate treatment.
  • Assessment of apoptosis sensitivity upon CTMP overexpression.
  • Analysis of protein-protein interactions involving CTMP and Hsp70.

Main Results:

  • CTMP localizes to mitochondria.
  • CTMP undergoes phosphorylation at Ser37 and Ser38 in response to insulin-mimetic treatment.
  • CTMP associates with heat shock protein 70 (Hsp70), inhibiting the formation of the Apaf-1/Hsp70 complex.
  • Overexpression of CTMP enhances cellular sensitivity to apoptosis, linked to Hsp70 inhibition.

Conclusions:

  • Phosphorylation of CTMP at Ser37/Ser38 is critical for preventing its mitochondrial localization and promoting cell death via Hsp70 binding.
  • CTMP's role extends beyond PKB inhibition, significantly contributing to mitochondria-mediated apoptosis.
  • CTMP's mitochondrial localization is a key factor in its pro-apoptotic function.

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