Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P05109 (
S100A8
)
1,212
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
GDF-8
is a new member of the TGF-beta superfamily which appears to be a negative regulator of skeletal muscle mass. Factors which regulate the biological activity of
GDF-8
have not yet been identified. However, the biological activities of TGF-beta superfamily members, TGF-beta1, -beta2 and -beta3, can be inhibited by noncovalent association with TGF-beta1, -beta2 and beta3 propeptides cleaved from the amino-termini of the TGF-beta precursor proteins. In contrast, the propeptides of other TGF-beta superfamily members do not appear to be inhibitory. In this investigation, we demonstrate that purified recombinant
GDF-8
propeptide associates with purified recombinant
GDF-8
to form a noncovalent complex, as evidenced by size exclusion chromatography and chemical crosslinking analysis. Furthermore, we show that
GDF-8
propeptide inhibits the biological activity of
GDF-8
assayed on A204 rhabdomyosarcoma cells transfected with a (
CAGA
)12 reporter construct. Finally, we demonstrate that
GDF-8
propeptide inhibits specific
GDF-8
binding to L6 myoblast cells. Collectively, these data identify the
GDF-8
propeptide as an inhibitor of
GDF-8
biological activity.
...
PMID:GDF-8 propeptide binds to GDF-8 and antagonizes biological activity by inhibiting GDF-8 receptor binding. 1151 24
Myostatin (
GDF-8
) is known to negatively regulate skeletal muscle mass in myogenesis, but few studies have been conducted on the function of endogenous
GDF-8
in primary myoblasts. The present study was performed to assess the function of
GDF-8
by RNA interference using primary culture of chicken embryonic myoblasts in which myoblasts were differentiated into myotubes. An active form of small interfering RNA (siRNA-1) targeting
GDF-8
mRNA was introduced into myoblasts, and an inactive form of siRNA (siRNA-2) was used as a negative control.
GDF-8
transcript level was significantly reduced 24 h after the introduction of siRNA-1 to 25% of the control, whereas a 52-kDa
GDF-8
precursor was reduced to 45% of the control at 48 h. However, siRNA-2 did not decrease
GDF-8
transcript level. When
GDF-8
-mediated promoter activity was measured chronologically by means of a pGL(
CAGA
)(10)-constructed luciferase reporter assay, a concomitant change in activity was initiated after 24 h. The activity rapidly decreased 30 h after siRNA-1 introduction, whereas high activity was maintained at 30-42 h in the control and siRNA-2-treated myoblasts. Myogenic factors such as MyoD and p21, but not myogenin, were altered after 72 h. Cell fusion of the multinucleated myotubes was delayed by the siRNA-1 introduction, and myotubes with aggregated nuclei were shorter and wider. These results strongly suggest that deficiency of
GDF-8
delays cell differentiation and causes great alterations in the cellular morphology of chicken embryonic myotubes.
...
PMID:Gene silencing of myostatin in differentiation of chicken embryonic myoblasts by small interfering RNA. 1661 34
