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Updated: Oct 22, 2025

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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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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Non-canonical phosphorylation of Bmf by p38 MAPK promotes its apoptotic activity in anoikis

Zhe Zhi1, Zhenlin Ouyang2, Yibo Ren1

  • 1Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.

Cell Death and Differentiation
|August 31, 2021
PubMed

Insights

Cell detachment triggers p38 MAPK activation, which phosphorylates Bmf, promoting anoikis. This study reveals Bmf’s structural regulation during anchorage-loss-induced cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Bmf (Bcl-2-associated фильм) mediates anoikis by translocating to mitochondria upon cell detachment.
  • The mechanisms governing Bmf’s cytoskeletal tethering and release during anoikis were previously unclear.

Purpose of the Study:

  • To elucidate the structural basis of Bmf’s cytoskeletal interaction and its regulation during anoikis.
  • To identify the signaling pathways controlling Bmf release upon loss of cell adhesion.

Main Methods:

  • Utilized mammary epithelial cell lines and a knock-in mouse model.
  • Employed p38 MAPK signaling inhibition, Bmf knockdown, and crystallographic studies.
  • Investigated Bmf phosphorylation at threonine 72 (T72) and its impact on DLC2 binding.

Main Results:

  • Cell detachment rapidly activated p38 MAPK, which phosphorylates Bmf at T72.
  • Phosphorylation of Bmf T72 disrupts its interaction with DLC2 via steric hindrance.
  • Inhibition of p38 MAPK or Bmf knockdown prevented anoikis.
  • Phosphomimetic mutation of T72 increased Bmf’s apoptotic activity.

Conclusions:

  • Discovered a novel regulatory mechanism for Bmf activity during anoikis involving p38 MAPK-mediated phosphorylation.
  • Provided structural insights into Bmf’s cytoskeletal tethering and release, crucial for anoikis initiation.

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