Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1

Christopher M Tracy1, Amy J Gray, Jorge Cuéllar

  • 1From the Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602.

Insights

Programmed cell death protein 5 (PDCD5) inhibits beta-tubulin folding by interacting with the CCT chaperone. This interaction may explain PDCD5's role as a tumor suppressor and pro-apoptotic factor.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Programmed cell death protein 5 (PDCD5) is implicated as a tumor suppressor and pro-apoptotic factor.
  • The precise mechanisms of PDCD5's apoptotic function remain largely unelucidated.
  • The cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) is essential for protein folding.

Purpose of the Study:

  • To investigate the molecular mechanisms by which PDCD5 exerts its pro-apoptotic function.
  • To identify binding partners of phosducin-like protein and their role in CCT-mediated protein folding.

Main Methods:

  • Proteomics analysis to identify PDCD5-CCT interactions.
  • Biochemical assays to assess the effect of PDCD5 on beta-tubulin folding.
  • Cryo-electron microscopy to visualize the PDCD5-CCT complex structure.

Main Results:

  • PDCD5 was found to interact with CCT and specifically inhibit the folding of its substrate, beta-tubulin.
  • Cryo-electron microscopy revealed that PDCD5 binds to the CCTβ apical domain, sterically hindering beta-tubulin binding.
  • This steric hindrance suggests a mechanism by which PDCD5 inhibits beta-tubulin folding.

Conclusions:

  • PDCD5 inhibits beta-tubulin folding through steric interference with the CCT chaperone.
  • This inhibition of beta-tubulin folding likely contributes to PDCD5's role in apoptosis and tumor suppression.
  • Targeting tubulin folding represents a potential therapeutic strategy in cancer treatment.

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