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: UMLS:C0376358 (
prostate cancer
)
59,338
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sentrin/SUMO (small ubiquitin-like modifier)-specific proteases (SENPs) have been implicated in the development of
prostate cancer
. However, due to the low abundance of SUMO-modified proteins and high activity of SENPs, the SUMO substrates affected by SENPs in
prostate cancer
cells are largely unknown. Here, we identified SI2, a novel cell-permeable SENP-specific inhibitor, by high-throughput screening. Using SI2 as a way of inhibiting the activity of SENPs and the SUMO stably transfected PC3 cells as a
prostate cancer
model, in combination with the stable isotope labeling with amino acids (SILAC) quantitative proteomic technique, we identified more than 900 putative target proteins of SUMO, in which 231 proteins were further subjected to bioinformatic analysis. In the highly enriched spliceosome pathway, we validated that
USP39
, HSPA1A, and HSPA2 were novel target proteins of SUMO. Furthermore, we demonstrated that K6, K16, K29, K51, and K73 were the SUMOylation sites of
USP39
. Mutation of these SUMO modification sites of
USP39
further promoted the proliferation-enhancing effect of
USP39
on
prostate cancer
cells. This study provides the SUMOproteome of PC3 cells and reveals that SUMOylation of spliceosome factors may be implicated in the pathogenesis of
prostate cancer
. Optimization of SI2 for isotype-specific SENP inhibitors warrants further investigation.
...
PMID:Important role of SUMOylation of Spliceosome factors in prostate cancer cells. 2502 93
