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 journalArticle

6 Scopus citations

Abstract

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
Volume25
Issue number2
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Dai, H., Ding, H., Peterson, K. L., Meng, X. W., Schneider, P. A., Knorr, K. L. B., & Kaufmann, S. H. (2018). Measurement of BH3-only protein tolerance. Cell Death and Differentiation, 25(2), 282-293. https://doi.org/10.1038/cdd.2017.156