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:3.4.22.61 (
caspase-8
)
6,833
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The formation of a heterodimer between Huntingtin-interacting protein-1 (HIP-1) and its novel partner
HIPPI
(HIP-1 protein interactor) through their pseudo death-effector domains (pDEDs) is a key step that recruits
caspase-8
and initiates apoptosis. This could be one of the pathways by which apoptosis is increased in Huntington's disease (HD). A construct consisting of the pDED of
HIPPI
has been cloned and overexpressed as 6NH-tagged protein and purified by Ni-NTA affinity chromatography. Crystals of the pDED of
HIPPI
were grown in space group P4(1), with unit-cell parameters a = b = 77.42, c = 33.31 A and a calculated Matthews coefficient of 1.88 A3 Da(-1) (33% solvent content) with two molecules per asymmetric unit.
...
PMID:Cloning, expression, purification, crystallization and preliminary crystallographic analysis of pseudo death-effector domain of HIPPI, a molecular partner of Huntingtin-interacting protein HIP-1. 1714 8
To investigate the mechanism of increased expression of caspase-1 caused by exogenous Hippi, observed earlier in HeLa and Neuro2A cells, in this work we identified a specific motif AAAGACATG (- 101 to - 93) at the caspase-1 gene upstream sequence where
HIPPI
could bind. Various mutations in this specific sequence compromised the interaction, showing the specificity of the interactions. In the luciferase reporter assay, when the reporter gene was driven by caspase-1 gene upstream sequences (- 151 to - 92) with the mutation G to T at position - 98, luciferase activity was decreased significantly in green fluorescent protein-Hippi-expressing HeLa cells in comparison to that obtained with the wild-type caspase-1 gene 60 bp upstream sequence, indicating the biological significance of such binding. It was observed that the C-terminal 'pseudo' death effector domain of
HIPPI
interacted with the 60 bp (- 151 to - 92) upstream sequence of the caspase-1 gene containing the motif. We further observed that expression of
caspase-8
and caspase-10 was increased in green fluorescent protein-Hippi-expressing HeLa cells. In addition,
HIPPI
interacted in vitro with putative promoter sequences of these genes, containing a similar motif. In summary, we identified a novel function of
HIPPI
; it binds to specific upstream sequences of the caspase-1,
caspase-8
and caspase-10 genes and alters the expression of the genes. This result showed the motif-specific interaction of
HIPPI
with DNA, and indicates that it could act as transcription regulator.
...
PMID:Interactions of HIPPI, a molecular partner of Huntingtin interacting protein HIP1, with the specific motif present at the putative promoter sequence of the caspase-1, caspase-8 and caspase-10 genes. 1762 17
