Pin1-Induced Proline Isomerization in Cytosolic p53 Mediates BAX Activation and Apoptosis

Ariele Viacava Follis, Fabien Llambi, Parker Merritt, Jerry E. Chipuk, Douglas R. Green, Richard W. Kriwacki

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)677-684
Number of pages8
JournalMolecular Cell
Volume59
Issue number4
DOIs
StatePublished - 20 Aug 2015

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