TY - JOUR
T1 - Measurement of BH3-only protein tolerance
AU - Dai, Haiming
AU - Ding, Husheng
AU - Peterson, Kevin L.
AU - Meng, X. Wei
AU - Schneider, Paula A.
AU - Knorr, Katherine L.B.
AU - Kaufmann, Scott H.
N1 - Publisher Copyright:
© 2018 ADMC Associazione Differenziamentoe.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
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U2 - 10.1038/cdd.2017.156
DO - 10.1038/cdd.2017.156
M3 - Article
C2 - 29053140
AN - SCOPUS:85047993135
SN - 1350-9047
VL - 25
SP - 282
EP - 293
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 2
ER -