Journal article

Bid chimeras indicate that most BH3-only proteins can directly activate Bak and Bax, and show no preference for Bak versus Bax

C Hockings, K Anwari, RL Ninnis, J Brouwer, M O'Hely, M Evangelista, MG Hinds, PE Czabotar, EF Lee, WD Fairlie, G Dewson, RM Kluck

CELL DEATH & DISEASE | NATURE PUBLISHING GROUP | Published : 2015

Abstract

The mitochondrial pathway of apoptosis is initiated by Bcl-2 homology region 3 (BH3)-only members of the Bcl-2 protein family. On upregulation or activation, certain BH3-only proteins can directly bind and activate Bak and Bax to induce conformation change, oligomerization and pore formation in mitochondria. BH3-only proteins, with the exception of Bid, are intrinsically disordered and therefore, functional studies often utilize peptides based on just their BH3 domains. However, these reagents do not possess the hydrophobic membrane targeting domains found on the native BH3-only molecule. To generate each BH3-only protein as a recombinant protein that could efficiently target mitochondria, w..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Association for International Cancer Research


Awarded by Worldwide Cancer Research


Funding Acknowledgements

We thank Jerry Adams for critical reading of the manuscript; Stephanie Fennell, Tobias Kratina and Ahmad Wardak for technical assistance; Adeline Robin and Michael Roy for recombinant proteins; David Huang for ABT-737. The work was supported by grants from the National Health and Medical Research Council of Australia (no. 575559, no. 1016701 and no. 1041936), and the Association for International Cancer Research (no. 10-230), and operational infrastructure grants through the Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC IRIISS.