Srinivasa M. Srinivasula;Ramesh Hegde;Ayman Saleh;Pinaki Datta;Eric Shiozaki;继杰 柴;Ryung Ah Lee;Paul D. Robbins;Teresa Fernandes-Alnemri;一公 施;Emad S. Alnemri
Thomas Jefferson University;University of Pittsburgh;Princeton University
发表时间:2001-3-1
期 刊:Nature
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=0035282570&partnerID=8YFLogxK
X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspase-9 and inhibits its activity, whereas Smac (also known as DIABLO) relieves this inhibition through interaction with XIAP. Here we show that XIAP associates with the active caspase-9-Apaf-1 holoenzyme complex through binding to the amino terminus of the linker peptide on the small subunit of caspase-9, which becomes exposed after proteolytic processing of procaspase-9 at Asp 315. Supporting this observation, point mutations that abrogate the proteolytic processing but not the catalytic activity of caspase-9, or deletion of the linker peptide, prevented caspase-9 association with XIAP and its concomitant inhibition. We note that the N-terminal four residues of caspase-9 linker peptide share significant homology with the N-terminal tetra-peptide in mature Smac and in the Drosophila proteins Hid/Grim/Reaper, defining a conserved class of IAP-binding motifs. Consistent with this finding, binding of the caspase-9 linker peptide and Smac to the BIR3 domain of XIAP is mutually exclusive, suggesting that Smac potentiates caspase-9 activity by disrupting the interaction of the linker peptide of caspase-9 with BIR3. Our studies reveal a mechanism in which binding to the BIR3 domain by two conserved peptides, one from Smac and the other one from caspase-9, has opposing effects on caspase activity and apoptosis.
Scopus度量
年份 | CiteScore | SJR | SNIP |
---|---|---|---|
1996 | |||
1997 | |||
1998 | |||
1999 | 15.599 | 7.187 | |
2000 | 11.917 | 6.857 | |
2001 | 9.874 | 6.767 | |
2002 | 10.114 | 7.184 | |
2003 | 11.384 | 7.492 | |
2004 | 11.222 | 7.538 | |
2005 | 10.333 | 7.199 | |
2006 | 9.702 | 7.156 | |
2007 | 10.344 | 7.097 | |
2008 | 13.17 | 7.307 | |
2009 | 15.185 | 8.234 | |
2010 | 16.465 | 8.204 | |
2011 | 53.1 | 17.598 | 8.667 |
2012 | 51 | 17.546 | 8.409 |
2013 | 50.9 | 19.69 | 8.511 |
2014 | 49.9 | 18.78 | 7.918 |
2015 | 51.6 | 19.669 | 8.08 |
2016 | 49.2 | 18.389 | 7.901 |
2017 | 53.7 | 17.875 | 8.679 |
2018 | 55.7 | 16.345 | 9.448 |
2019 | 51 | 14.047 | 8.546 |
2020 | 56.9 | 15.993 | 9.249 |
2021 | 56 |
相似文献推荐