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Related Experiment Video

Updated: Jul 5, 2026

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

Multisite phosphorylation regulates Bim stability and apoptotic activity.

Anette Hübner1, Tamera Barrett, Richard A Flavell

  • 1Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Molecular Cell
|May 24, 2008
PubMed
Summary
This summary is machine-generated.

Investigating Bim protein phosphorylation in mice revealed that altering specific sites impacts cell death regulation. Phosphorylation changes affect Bim binding to Bcl2 and its degradation, influencing cell survival and apoptosis sensitivity.

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Last Updated: Jul 5, 2026

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

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The BH3-only protein Bim is a key regulator of apoptosis (programmed cell death).
  • Multisite phosphorylation of Bim by MAP kinases is a known regulatory mechanism controlling its apoptotic function.
  • Understanding Bim phosphorylation's in vivo role is crucial for deciphering cell death signaling pathways.

Purpose of the Study:

  • To investigate the in vivo functional consequences of Bim phosphorylation.
  • To elucidate how specific phosphorylation sites on Bim modulate its interaction with Bcl2 and its degradation.
  • To determine the contribution of differential Bim phosphorylation to cellular apoptotic responses.

Main Methods:

  • Generation of mice expressing phosphorylation-defective Bim mutant proteins.
  • Analysis of Bim binding affinity to the antiapoptotic protein Bcl2.
  • Assessment of Bim protein stability and proteasomal degradation rates.
  • Evaluation of cellular apoptosis sensitivity in response to Bim mutations.

Main Results:

  • Mutation of the Thr-112 phosphorylation site reduced Bim binding to Bcl2, leading to increased cell survival.
  • Mutations at Ser-55, Ser-65, and Ser-73 sites resulted in increased apoptosis due to impaired proteasomal degradation of Bim.
  • These findings demonstrate distinct roles for different Bim phosphorylation sites.

Conclusions:

  • Bim phosphorylation regulates its apoptotic activity through multiple mechanisms.
  • Phosphorylation of different Bim sites differentially impacts its interaction with Bcl2 and its degradation.
  • These phosphorylation-dependent regulatory events are critical determinants of cellular sensitivity to apoptosis.