Journal
MOLECULAR CELL
Volume 59, Issue 4, Pages 677-684Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2015.06.029
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Funding
- NIH [R01CA082491, 1R01GM083159, R01GM52735, R01GM96208, R01CA157740]
- American Cancer Society Research Scholar Award
- National Cancer Institute Cancer Center Support Grant [P30CA21765]
- ALSAC
- Neoma Boadway Fellowship from SJCRH
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The cytosolic fraction of the tumor suppressor p53 activates the apoptotic effector protein BAX to trigger apoptosis. Here we report that p53 activates BAX through a mechanism different from that associated with activation by BH3 only proteins (BIM and BID). We observed that cis-trans isomerization of proline 47 (Pro47) within p53, an inherently rare molecular event, was required for BAX activation. The prolyl isomerase Pin1 enhanced p53-dependent BAX activation by catalyzing cis-trans interconversion of p53 Pro47. Our results reveal a signaling mechanism whereby proline cis-trans isomerization in one protein triggers conformational and functional changes in a downstream signaling partner. Activation of BAX through the concerted action of cytosolic p53 and Pin1 may integrate cell stress signals to induce a direct apoptotic response.
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