Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis.
摘要：
The elimination of Mcl-1, an anti-apoptotic Bcl-2 family member, is an early and required step for DNA damage-induced apoptosis. The degradation of Mcl-1 can be blocked by proteasome inhibitors, suggesting a role for the ubiquitin proteasome pathway in apoptosis. Here, we demonstrate that Mcl-1 is ubiquinated at five lysines. Biochemical fractionation of cell extracts allowed us to identify a 482 kDa HECT-domain-containing ubiquitin ligase named Mule (Mcl-1 ubiquitin ligase E3) that is both required and sufficient for the polyubiquitination of Mcl-1. Mule also contains a region similar to the Bcl-2 homology region 3 (BH3) domain that allows Mule to specifically interact with Mcl-1. Elimination of Mule expression by RNA interference stabilizes Mcl-1 protein, resulting in an attenuation of the apoptosis induced by DNA-damage agents. Thus, Mule is a unique BH3-containing E3 ubiquitin ligase apical to Bcl-2 family proteins during DNA damage-induced apoptosis.
展开
关键词：
Animals Humans Ubiquitin-Protein Ligases Neoplasm Proteins Proto-Oncogene Proteins c-bcl-2 Catalytic Domain Apoptosis RNA Interference Amino Acid Sequence Molecular Sequence Data
DOI：
10.1016/j.cell.2005.06.009
被引量：
年份：
2005
Elsevier
(全网免费下载)
Elsevier
掌桥科研
万方医学
Semantic Scholar
(全网免费下载)
查看更多
dx.doi.org
NCBI
NCBI
Cell Press
(全网免费下载)
Cell Press
Europe PMC
ResearchGate
(全网免费下载)
ResearchGate
EBSCO
scienceopen.com
core.ac.uk
(全网免费下载)
utsouthwestern.influuent.utsystem.edu
hw-f5-embomm.highwire.org
neoplasia.com
mendeley.com
onAcademic
embor.embopress.org
jcs.biologists.org
mcb.berkeley.edu
(全网免费下载)
molbiolcell.org
haematologica.org
pubget.com
f1000.com
infona.pl
mct.aacrjournals.org
deepdyve.com
cghjournal.org
mysciencework.com
readcube.com
science-open.com
Elsevier
(全网免费下载)
Semantic Scholar
(全网免费下载)
Cell Press
(全网免费下载)
ResearchGate
(全网免费下载)
mcb.berkeley.edu
(全网免费下载)
core.ac.uk
(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！
