Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function.
摘要：
Apoptosis is initiated when Bcl-2 and its prosurvival relatives are engaged by proapoptotic BH3-only proteins via interaction of its BH3 domain with a groove on the Bcl-2-like proteins. These interactions have been considered promiscuous, but our analysis of the affinity of eight BH3 peptides for five Bcl-2-like proteins has revealed that the interactions vary over 10,000-fold in affinity, and accordingly, only certain protein pairs associate inside cells. Bim and Puma potently engaged all the prosurvival proteins comparably. Bad, however, bound tightly to Bcl-2, Bcl-x L, and Bcl-w but only weakly to A1 and not to Mcl-1. Strikingly, Noxa bound only Mcl-1 and A1. In accord with their complementary binding, Bad and Noxa cooperated to induce potent killing. The results suggest that apoptosis relies on selective interactions between particular subsets of these proteins and that it should be feasible to discover BH3-mimetic drugs that inactivate specific prosurvival targets.
展开
DOI：
10.1016/j.molcel.2004.12.030
被引量：
年份：
2005
Elsevier
(全网免费下载)
Elsevier
万方医学
Semantic Scholar
(全网免费下载)
掌桥科研
查看更多
dx.doi.org
Europe PMC
BioMed Central
Cell Press
NCBI
Cell Press
(全网免费下载)
Cell Press
(全网免费下载)
NCBI
dialnet.unirioja.es
ResearchGate
(全网免费下载)
ResearchGate
EBSCO
Citeseer
(全网免费下载)
EBSCO
abstracts.hematologylibrary.org
readcube.com
cnc.cj.uc.pt
(全网免费下载)
reproduction-online.org
jacionline.org
deepdyve.com
haematologica.org
jcs.biologists.org
f1000.com
ajpcell.physiology.org
infona.pl
neoplasia.com
hw-f5-msb.highwire.org
science-open.com
mysciencework.com
scienceopen.com
mct.aacrjournals.org
arrow.latrobe.edu.au:8080
yadda.icm.edu.pl
(全网免费下载)
molbiolcell.org
www.socolar.com
cghjournal.org
ukpmc.ac.uk
msb.embopress.org
Elsevier
(全网免费下载)
Semantic Scholar
(全网免费下载)
Cell Press
(全网免费下载)
Cell Press
(全网免费下载)
ResearchGate
(全网免费下载)
Citeseer
(全网免费下载)
yadda.icm.edu.pl
(全网免费下载)
cnc.cj.uc.pt
(全网免费下载)
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
