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: UMLS:C0017636 (
glioblastoma
)
18,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Using a suppressive subtractive hybridization system, we identified
CSIG
(
cellular senescence-inhibited gene protein
; RSL1D1) that was abundant in young human diploid fibroblast cells but declined upon replicative senescence. Overexpression or knockdown of
CSIG
did not influence p21(Cip1) and p16(INK4a) expressions. Instead,
CSIG
negatively regulated PTEN and p27(Kip1) expressions, in turn promoting cell proliferation. In PTEN-silenced HEK 293 cells and PTEN-deficient human
glioblastoma
U87MG cells, the effect of
CSIG
on p27(Kip1) expression and cell division was abolished, suggesting that PTEN was required for the role of
CSIG
on p27(Kip1) regulation and cell cycle progression. Investigation into the underlying mechanism revealed that the regulation of PTEN by
CSIG
was achieved through a translational suppression mechanism. Further study showed that
CSIG
interacted with PTEN mRNA in the 5' untranslated region (UTR) and that knockdown of
CSIG
led to increased luciferase activity of a PTEN 5' UTR-luciferase reporter. Moreover, overexpression of
CSIG
significantly delayed the progression of replicative senescence, while knockdown of
CSIG
expression accelerated replicative senescence. Knockdown of PTEN diminished the effect of
CSIG
on cellular senescence. Our findings indicate that
CSIG
acts as a novel regulatory component of replicative senescence, which requires PTEN as a mediator and involves in a translational regulatory mechanism.
...
PMID:CSIG inhibits PTEN translation in replicative senescence. 1867 45
