BID Preferentially Activates BAK While BIM Preferentially Activates BAX, Affecting Chemotherapy Response

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Oct 1

PMID 24074954

Citations 137

Authors

Kristopher A Sarosiek

Xiaoke Chi

John A Bachman

Joshua J Sims

Joan Montero

Luv Patel

Annabelle Flanagan

David W Andrews

Peter Sorger

Anthony Letai

Affiliations

Soon will be listed here.

Abstract

Apoptosis is a highly regulated form of cell death that controls normal homeostasis as well as the antitumor activity of many chemotherapeutic agents. Commitment to death via the mitochondrial apoptotic pathway requires activation of the mitochondrial pore-forming proteins BAK or BAX. Activation can be effected by the activator BH3-only proteins BID or BIM, which have been considered to be functionally redundant in this role. Herein, we show that significant activation preferences exist between these proteins: BID preferentially activates BAK while BIM preferentially activates BAX. Furthermore, we find that cells lacking BAK are relatively resistant to agents that require BID activation for maximal induction of apoptosis, including topoisomerase inhibitors and TRAIL. Consequently, patients with tumors that harbor a loss of BAK1 exhibit an inferior response to topoisomerase inhibitor treatment in the clinic. Therefore, BID and BIM have nonoverlapping roles in the induction of apoptosis via BAK and BAX, affecting chemotherapy response.

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