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:2.5.1.18 (
glutathione S-transferase
)
22,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The heterodimeric hypoxia-inducible transcription factors (HIFs) are central regulators of the response to low oxygenation. HIF-alpha subunits are constitutively expressed but rapidly degraded under normoxic conditions. Oxygen-dependent hydroxylation of two conserved prolyl residues by prolyl-4-hydroxylase domain-containing enzymes (PHDs) targets HIF-alpha for proteasomal destruction. We identified the peptidyl prolyl cis/trans isomerase
FK506-binding protein 38
(
FKBP38
) as a novel interactor of PHD2. Yeast two-hybrid,
glutathione S-transferase
pull-down, coimmunoprecipitation, colocalization, and mammalian two-hybrid studies confirmed specific
FKBP38
interaction with PHD2, but not with PHD1 or PHD3. PHD2 and
FKBP38
associated with their N-terminal regions, which contain no known interaction motifs. Neither
FKBP38
mRNA nor protein levels were regulated under hypoxic conditions or after PHD inhibition, suggesting that
FKBP38
is not a HIF/PHD target. Stable RNA interference-mediated depletion of
FKBP38
resulted in increased PHD hydroxylation activity and decreased HIF protein levels and transcriptional activity. Reconstitution of
FKBP38
expression abolished these effects, which were independent of the peptidyl prolyl cis/trans isomerase activity. Downregulation of
FKBP38
did not affect PHD2 mRNA levels but prolonged PHD2 protein stability, suggesting that
FKBP38
is involved in PHD2 protein regulation.
...
PMID:The peptidyl prolyl cis/trans isomerase FKBP38 determines hypoxia-inducible transcription factor prolyl-4-hydroxylase PHD2 protein stability. 1735 76
The non-structural 5A (NS5A) protein of classical swine fever virus (CSFV) is proven to be involved in viral replication and can also modulate cellular signaling and host cellular responses via to its ability to interact with various cellular proteins.
FKBP8
is also reported to promote virus replication. Here, we show that NS5A specifically interacts with
FKBP8
through coimmunoprecipitation and
GST
-pulldown studies. Additionally, confocal microscopy study showed that NS5A and
FKBP8
colocalized in the cytoplasm. Overexpression of
FKBP8
via the eukaryotic expression plasmid pDsRED N1 significantly promoted viral RNA synthesis. The cells knockdown of
FKBP8
by lentivirus-mediated shRNA markedly decreased the virus replication when infected with CSFV. These data suggest that
FKBP8
plays a critical role in the viral life cycle, particularly during the virus RNA replication period. The investigation of
FKBP8 protein
functions may be beneficial for developing new strategies to treat CSFV infection.
...
PMID:FKBP8 interact with classical swine fever virus NS5A protein and promote virus RNA replication. 2674 56
Mitophagy is a conserved intracellular catabolic process responsible for the selective removal of dysfunctional or superfluous mitochondria to maintain mitochondrial quality and need in cells. Here, we examine the mechanisms of receptor-mediated mitophagy activation, with the focus on BNIP3L/NIX mitophagy receptor, proven to be indispensable for selective removal of mitochondria during the terminal differentiation of reticulocytes. The molecular mechanisms of selecting damaged mitochondria from healthy ones are still very obscure. We investigated BNIP3L dimerization as a potentially novel molecular mechanism underlying BNIP3L-dependent mitophagy. Forming stable homodimers, BNIP3L recruits autophagosomes more robustly than its monomeric form. Amino acid substitutions of key transmembrane residues of BNIP3L, BNIP3L
G204A
or BNIP3L
G208V
, led to the abolishment of dimer formation, resulting in the lower LC3A-BNIP3L recognition and subsequently lower mitophagy induction. Moreover, we identified the serine 212 as the main amino acid residue at the C-terminal of BNIP3L, which extends to the intermembrane space, responsible for dimerization. In accordance, the phosphomimetic mutation BNIP3L
S212E
leads to a complete loss of BNIP3L dimerization. Thus, the interplay between BNIP3L phosphorylation and dimerization indicates that the combined mechanism of LIR phosphorylation and receptor dimerization is needed for proper BNIP3L-dependent mitophagy initiation and progression.
Abbreviations:
AMBRA1: autophagy and beclin 1 regulator 1; Baf A1: bafilomycin A
1
; BH3: BCL2 homology 3; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; CoCl
2
: cobalt (II) chloride;
FKBP8
: FKBP prolyl isomerase 8; FUNDC1: FUN14 domain containing 1; GABARAP: GABA type A receptor-associated protein;
GST
:
glutathione S-transferase
; IMM: inner mitochondrial membrane; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OMM: outer mitochondrial membrane; PHB2: prohibitin 2; PI: propidium iodide; PINK1: PTEN induced kinase 1; TM: transmembrane domain; TOMM20: translocase of outer mitochondrial membrane 20.
...
PMID:Dimerization of mitophagy receptor BNIP3L/NIX is essential for recruitment of autophagic machinery. 3228 18
