Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:1.2.1.13 (
glyceraldehyde-3-phosphate dehydrogenase
)
6,511
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glyceraldehyde-3-phosphate dehydrogenase (
GAPDH
; E.C. 1.2.1.12) functions as a glycolytic enzyme within the cytoplasm, but beside its metabolic function it is involved in early steps of apoptosis, which trigger the translocation of
GAPDH
into the nucleus. As apoptosis can be induced by serum withdrawal, which otherwise causes cell cycle arrest, the linkage between serum deprivation, cell cycle and nuclear transport of
GAPDH
has been investigated. The intracellular distribution of
GAPDH
was monitored by confocal laser scanning microscopy of either immuno-stained NIH 3T3 fibroblasts or of cells overexpressing GFP-tagged
GAPDH
. Serum withdrawal led to an accumulation of
GAPDH
in the nucleus. In contrast to investigations published so far, this nuclear translocation was a reversible process: cytoplasmic location of endogenous
GAPDH
or of GFP-
GAPDH
could be recovered upon serum addition to arrested cells and was not inhibited by cycloheximide treatment. In addition, the nuclear import upon serum depletion had no influence neither on the catalytic activity nor on the expression level of
GAPDH
. The nuclear export of GFP-
GAPDH
in serum-deprived cells could be stimulated by serum or directly by the growth factors EGF or PDGE The transport process is not regulated via an initiation of cell cycle arrest, as olomoucine, which causes G1-arrest neither stimulated nuclear accumulation nor prevented nuclear export after serum addition to serum-depleted cultures. Moreover, SV40-transformed 3T3 cells transported
GAPDH
into the nucleus upon serum deprivation, though the expression of the viral large T-antigen enabled growth factor-independent cell proliferation in this cell line. The recruitment of
GAPDH
to the cytoplasm upon serum stimulation of arrested cells was not impaired by the inhibition of the MAPK signalling pathway with PD 098059. However, further analysis of the growth factor signalling pathway with specific inhibitors revealed that nuclear export was prevented by
LY 294002
, an inhibitor of the PI-3 kinase. PI3K links the growth factor signalling pathway with cell death via the repression of an apoptotic inducer. Thus, the nuclear accumulation of
GAPDH
upon growth factor depletion is a reversible process not related directly to cell cycle and likely triggered by survival signals.
...
PMID:Reversible nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase upon serum depletion. 1148 33
In addition to its well-known glycolytic activity,
GAPDH
displays multiple functions, such as nuclear RNA export, DNA replication and repair, and apoptotic cell death. This functional diversity depends on its intracellular localization. In this study, we explored the signal transduction pathways involved in the nuclear translocation of
GAPDH
using confocal laser scanning microscopy of immunostained human diploid fibroblasts (HDFs).
GAPDH
was present mainly in the cytoplasm when cultured with 10% FBS. Serum depletion by culturing cells in a serum-free medium (SFM) led to a gradual accumulation of
GAPDH
in the nucleus, and this nuclear accumulation was reversed by the re-addition of serum or growth factors, such as PDGF and lysophosphatidic acid. The nuclear export induced by the re-addition of serum or growth factors was prevented by
LY 294002
and SH-5, inhibitors of phosphoinositide 3-kinase (PI3K) and Akt/protein kinase B, respectively, suggesting an involvement of the PI3K signaling pathway in the nuclear export of
GAPDH
. In addition, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK), stimulated the nuclear translocation of
GAPDH
and prevented serum- and growth factor-induced
GAPDH
export. AMPK inhibition by compound C or AMPK depletion by siRNA treatment partially prevented SFM- and AICAR-induced nuclear translocation of
GAPDH
. Our data suggest that the nuclear translocation of
GAPDH
might be regulated by the PI3K signaling pathway acting mainly as a nuclear export signal and the AMPK signaling pathway acting as a nuclear import signal.
...
PMID:Activation of AMP-activated protein kinase stimulates the nuclear localization of glyceraldehyde 3-phosphate dehydrogenase in human diploid fibroblasts. 2017 50
