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Literature summary for 1.14.19.17 extracted from

  • McNaughton, M.; Pitman, M.; Pitson, S.M.; Pyne, N.J.; Pyne, S.
    Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells (2016), Oncotarget, 7, 16663-16675 .
    View publication on PubMedView publication on EuropePMC
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Inhibitors

Inhibitors Comment Organism Structure
2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole SKi, a SK1/SK2 inhibitor Homo sapiens
3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide i.e. ABC294640 Homo sapiens
fenretinide the Des1 inhibitor induces a reduction in SK1a expression and an increase in p53 and p21 expression Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
JURKAT cell
-
 Homo sapiens
-
LNCaP-AI cell
-
 Homo sapiens
-
prostate cancer cell
-
 Homo sapiens
-

Subunits

Subunits Comment Organism
? x * 38000, SDS-PAGE Homo sapiens

Synonyms

Synonyms Comment Organism
DES1
-
 Homo sapiens
dihydroceramide desaturase
-
 Homo sapiens

General Information

General Information Comment Organism
malfunction inhibitors SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 in LNCaP-AI prostate cancer cells. Inhibitors SKi, ABC294640, or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 fails to increase p53 and p21 expression, but the former reduces DNA synthesis in LNCaP-AI prostate cancer cells. N-acetylcysteine (reactive oxygen species scavenger) blocks the SK inhibitor-induced increase in p21 and p53 expression but has no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increases p53 expression while a combination of Des1/SK1 siRNA increases the expression of p21. Modulation of both de novo and sphingolipid rheostat pathways in order to induce growth arrest can be achived by targeting androgen-independent prostate cancer cells with compounds that affect the enzymes Des1 and SK1. N-acetyl cysteine has no effect on the ABC294640-induced proteasomal degradation of Des1, suggesting that the oxidative stress response is down stream of Des1 Homo sapiens
metabolism enzymes Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways Homo sapiens