Measurement of BH3-only protein tolerance

Haiming Dai, Husheng Ding, Kevin L. Peterson, X. Wei Meng, Paula A. Schneider, Katherine L.B. Knorr, Scott H. Kaufmann

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The BCL2 family of proteins regulates cellular life and death decisions. Among BCL2 family members, BH3-only proteins have critical roles by neutralizing antiapoptotic family members, as well as directly activating BAX and BAK. Despite widespread occurrence of BH3-only protein upregulation in response to various stresses, this process is rarely quantified. Moreover, it is unclear whether all BH3-only proteins are equipotent at inducing cell death. Here we show that BH3-only proteins increase as much as 15- to 20-fold after various treatments and define a parameter, termed BH3-only tolerance, which measures how many copies of a particular BH3-only protein can be expressed before the majority of cells in a population undergo apoptosis. We not only assess the relative contributions of anti- and proapoptotic BCL2 family members to BH3-only tolerance, but also illustrate how the study of this parameter can be used to understand cellular sensitivity to anticancer drugs and new combinations. These observations provide a new quantitative framework for assessing apoptotic susceptibility under various conditions.

Original languageEnglish (US)
Pages (from-to)282-293
Number of pages12
JournalCell Death and Differentiation
Issue number2
StatePublished - 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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