Gene/Protein
Disease
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Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:3.4.22.62 (
caspase-9
)
7,507
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
p53 apoptosis effector related to PMP-22
(
PERP
) is a transcriptional target gene of p53 tumour suppressor that is specifically induced during apoptosis and not during cell cycle arrest. In primary uveal melanoma (UM), the most common intraocular malignancy in adults that has a reportedly unaffected signalling pathway upstream of and including p53,
PERP
expression is down-regulated in the metastatic monosomy 3-type tumours, compared with the less aggressive disomy 3-type tumours. Here, we demonstrate experimentally, by the use of full-length
PERP
-green fluorescent protein (GFP) fusions and real-time confocal microscopy, the intracellular targeting and plasma membrane localization of
PERP
in living UM cells and show that expression of
PERP
induces caspase-mediated apoptosis in UM cells. Induction of
PERP
expression in GFP-
PERP
-transfected UM cells leads to increased levels of cleaved caspase-8 forms, as well as to reduction of its full-length substrate Bid, but not to detectable processing of
caspase-9
. The levels of mature caspase-8, -9 and -3 proteins significantly correlate with
PERP
expression levels in primary UMs. Transcriptional profiling of
PERP
and caspase-8 in tumour specimens indicates that the positive association of
PERP
and caspase-8 proteins is a consequence of post-translational processing, most likely at the level of caspase-8 cleavage, and not of increased transcription of pro-caspase-8. We conclude that
PERP
expression leads to activation of an extrinsic receptor-mediated apoptotic pathway, with a possible subsequent engagement of the intrinsic apoptotic pathway. The findings underline the apoptotic pathway mediated by
PERP
as a critical mechanism employed by UM tumours to modulate susceptibility to apoptosis.
...
PMID:P53 apoptosis mediator PERP: localization, function and caspase activation in uveal melanoma. 1904 Apr 20
