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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
JURKAT cell | - |
Homo sapiens | - |
LNCaP-AI cell | - |
Homo sapiens | - |
prostate cancer cell | - |
Homo sapiens | - |
Subunits | Comment | Organism |
---|---|---|
? | x * 38000, SDS-PAGE | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
DES1 | - |
Homo sapiens |
dihydroceramide desaturase | - |
Homo sapiens |
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 |