Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.60 (
caspase-7
)
920
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To achieve swift cell demise during apoptosis, caspases cleave essential proteins for cell survival and removal. In addition to the binding of preferred amino acid sequences to its substrate-binding pocket,
caspase-7
also uses exosites to select specific substrates. 4 lysine residues (K
38
KKK) located in the N-terminal domain of
caspase-7
form such an exosite and promote the rapid proteolysis of the poly(ADP-ribose) polymerase 1 (PARP-1), but the mechanism of recognition remains mostly unknown. In this study, we show that the overall positive charge of the exosite is the critical feature of this evolutionarily conserved binding site. Additionally, interaction with the
caspase-7
exosite involves both the Zn3 and BRCT domains of PARP-1 and is mediated by RNA. Indeed, PARP-1 proteolysis efficacy is sensitive to
RNase A
and promoted by added RNA. Moreover, using affinity chromatography and gel shift assays, we demonstrate that
caspase-7
, but not caspase-3 or a
caspase-7
with a mutated exosite, binds nucleic acids. Finally, we show that
caspase-7
prefers RNA-binding proteins (RNA-BPs) as substrates compared to caspase-3 and that RNA enhances proteolysis by
caspase-7
of many of these RNA-BPs. Thus, we have uncovered an unusual way by which
caspase-7
selects and cleaves specific substrates.
...
PMID:Caspase-7 uses RNA to enhance proteolysis of poly(ADP-ribose) polymerase 1 and other RNA-binding proteins. 3158 28
