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Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function.

Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC.

Mol Cell. 2005 Feb 4;17(3):393-403.


A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation.

Lee EF, Czabotar PE, van Delft MF, Michalak EM, Boyle MJ, Willis SN, Puthalakath H, Bouillet P, Colman PM, Huang DC, Fairlie WD.

J Cell Biol. 2008 Jan 28;180(2):341-55. doi: 10.1083/jcb.200708096. Epub 2008 Jan 21.


Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands.

Day CL, Chen L, Richardson SJ, Harrison PJ, Huang DC, Hinds MG.

J Biol Chem. 2005 Feb 11;280(6):4738-44. Epub 2004 Nov 18.


Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity.

Wilson-Annan J, O'Reilly LA, Crawford SA, Hausmann G, Beaumont JG, Parma LP, Chen L, Lackmann M, Lithgow T, Hinds MG, Day CL, Adams JM, Huang DC.

J Cell Biol. 2003 Sep 1;162(5):877-87.


The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner.

Kazi A, Sun J, Doi K, Sung SS, Takahashi Y, Yin H, Rodriguez JM, Becerril J, Berndt N, Hamilton AD, Wang HG, Sebti SM.

J Biol Chem. 2011 Mar 18;286(11):9382-92. doi: 10.1074/jbc.M110.203638. Epub 2010 Dec 9.


BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly.

Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR, Newmeyer DD.

Mol Cell. 2005 Feb 18;17(4):525-35.


Determinants of BH3 binding specificity for Mcl-1 versus Bcl-xL.

Dutta S, Gullá S, Chen TS, Fire E, Grant RA, Keating AE.

J Mol Biol. 2010 May 21;398(5):747-62. doi: 10.1016/j.jmb.2010.03.058. Epub 2010 Apr 2.


Structural insights into the degradation of Mcl-1 induced by BH3 domains.

Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, Fairlie WD, Hinds MG, Colman PM.

Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22. Epub 2007 Mar 27.


A comparison of two strategies for affinity maturation of a BH3 peptide toward pro-survival Bcl-2 proteins.

Zhang S, Long A, Link AJ.

ACS Synth Biol. 2012 Mar 16;1(3):89-98. doi: 10.1021/sb200002m. Epub 2011 Oct 7.


The restricted binding repertoire of Bcl-B leaves Bim as the universal BH3-only prosurvival Bcl-2 protein antagonist.

Rautureau GJ, Yabal M, Yang H, Huang DC, Kvansakul M, Hinds MG.

Cell Death Dis. 2012 Dec 13;3:e443. doi: 10.1038/cddis.2012.178.


Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak.

Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P, Strasser A, Kluck RM, Adams JM, Huang DC.

Science. 2007 Feb 9;315(5813):856-9.


BH3 domains other than Bim and Bid can directly activate Bax/Bak.

Du H, Wolf J, Schafer B, Moldoveanu T, Chipuk JE, Kuwana T.

J Biol Chem. 2011 Jan 7;286(1):491-501. doi: 10.1074/jbc.M110.167148. Epub 2010 Nov 1.


Evaluation of diverse α/β-backbone patterns for functional α-helix mimicry: analogues of the Bim BH3 domain.

Boersma MD, Haase HS, Peterson-Kaufman KJ, Lee EF, Clarke OB, Colman PM, Smith BJ, Horne WS, Fairlie WD, Gellman SH.

J Am Chem Soc. 2012 Jan 11;134(1):315-23. doi: 10.1021/ja207148m. Epub 2011 Dec 8.


Mitochondrial permeabilization relies on BH3 ligands engaging multiple prosurvival Bcl-2 relatives, not Bak.

Uren RT, Dewson G, Chen L, Coyne SC, Huang DC, Adams JM, Kluck RM.

J Cell Biol. 2007 Apr 23;177(2):277-87.


Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins.

Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC.

Genes Dev. 2005 Jun 1;19(11):1294-305. Epub 2005 May 18.


In silico and in vitro elucidation of BH3 binding specificity toward Bcl-2.

London N, Gullá S, Keating AE, Schueler-Furman O.

Biochemistry. 2012 Jul 24;51(29):5841-50. doi: 10.1021/bi3003567. Epub 2012 Jul 12.


Mcl-1-Bim complexes accommodate surprising point mutations via minor structural changes.

Fire E, Gullá SV, Grant RA, Keating AE.

Protein Sci. 2010 Mar;19(3):507-19. doi: 10.1002/pro.329.


Selective involvement of BH3-only proteins and differential targets of Noxa in diverse apoptotic pathways.

Zhang L, Lopez H, George NM, Liu X, Pang X, Luo X.

Cell Death Differ. 2011 May;18(5):864-73. doi: 10.1038/cdd.2010.152. Epub 2010 Nov 26.


Bh3 induced conformational changes in Bcl-Xl revealed by crystal structure and comparative analysis.

Rajan S, Choi M, Baek K, Yoon HS.

Proteins. 2015 Jul;83(7):1262-72. doi: 10.1002/prot.24816. Epub 2015 May 23.


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