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Updated: Dec 29, 2025

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

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PEGylation-based strategy to identify pathways involved in the activation of apoptotic BAX protein

Yu-Jing Lan1, Yu-Ting Wang1, Chien-Lun Hung1

  • 1Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.

Biochimica Et Biophysica Acta. General Subjects
|January 29, 2020
PubMed
Abstract

Insights

This study reveals that BimBH3 peptides and cleaved Bid (cBid) protein activate BAX-mediated apoptosis through distinct pathways. A novel PEGylation approach differentiated these routes, showing BimBH3 targets the trigger groove and cBid engages the canonical groove.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • BAX activation is critical for initiating apoptosis.
  • The precise mechanisms by which different BAX activators, such as BimBH3 peptides and cleaved Bid (cBid), induce apoptosis are not fully understood.

Purpose of the Study:

  • To investigate and differentiate the molecular pathways utilized by BimBH3 peptides and cBid protein to activate BAX.
  • To explore the utility of a PEGylation-based approach in dissecting BAX activation mechanisms.

Main Methods:

  • Utilized a PEGylation-based strategy to selectively shield binding grooves on BAX.
  • Employed spectroscopic and biochemical techniques including electron spin resonance, circular dichroism, fluorescence recovery after photobleaching, and label-transfer assays.

Main Results:

  • A BAX mutant (164-PEG) exhibited differential responses to cBid and BimBH3.
  • BimBH3 directly binds the trigger groove (TG), causing α9 release from the canonical groove (CG) and oligomerization.
  • cBid interacts with the CG and requires mitochondrial lipids for full BAX activation.

Conclusions:

  • The PEGylation approach effectively differentiates BAX activation pathways.
  • Canonical groove (CG) engagement is essential for cBid-mediated BAX activation.
  • Identified distinct initiation pathways for BAX activation by cBid versus BimBH3 peptides.
Keywords:
ApoptosisBAXESRFRAPPEGylation

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