Capell-Hattam, Isabelle M.; Sharpe, Laura J.; Qian, Lydia; Hart-Smith, Gene; Prabhu, Anika V.; Brown, Andrew J. published the artcile< Twin enzymes, divergent control: the cholesterogenic enzymes DHCR14 and LBR are differentially regulated transcriptionally and post-translationally>, Safety of (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, the main research area is human cholesterol biosynthesis enzyme DHCR14 LBR post translational regulation; dehydrocholesterol reductase DHCR14 human regulation lamin B receptor LBR; DHCR14; LBR; TM7SF2; cholesterol; cholesterol regulation; endoplasmic reticulum-associated protein degradation (ERAD); enzyme degradation; protein degradation.
Cholesterol synthesis is a tightly regulated process, both transcriptionally and post-translationally. Transcriptional control of cholesterol synthesis is relatively well-understood. However, of the ~20 enzymes in cholesterol biosynthesis, post-translational regulation has only been examined for a small number Three of the four sterol reductases in cholesterol production, 7-dehydrocholesterol reductase (DHCR7), 14-dehydrocholesterol reductase (DHCR14), and lamin-B receptor (LBR), share evolutionary ties with a high level of sequence homol. and predicted structural homol. DHCR14 and LBR uniquely share the same Δ-14 reductase activity in cholesterol biosynthesis, yet little is known about their post-translational regulation. We have previously identified specific modes of post-translational control of DHCR7, but it is unknown whether these regulatory mechanisms are shared by DHCR14 and LBR. Using CHO-7 cells stably expressing epitope-tagged DHCR14 or LBR, we investigated the post-translational regulation of these enzymes. We found that DHCR14 and LBR undergo differential post-translational regulation, with DHCR14 being rapidly turned over, triggered by cholesterol and other sterol intermediates, whereas LBR remained stable. DHCR14 is degraded via the ubiquitin-proteasome system, and we identified several DHCR14 and DHCR7 putative interaction partners, including a number of E3 ligases that modulate DHCR14 levels. Interestingly, we found that gene expression across an array of human tissues showed a neg. relationship between the C14-sterol reductases; one enzyme or the other tends to be predominantly expressed in each tissue. Overall, our findings indicate that whereas LBR tends to be the constitutively active C14-sterol reductase, DHCR14 levels are tunable, responding to the local cellular demands for cholesterol.
Journal of Biological Chemistry published new progress about Follicular fluid. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Safety of (3S,9S,10R,13R,14R,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts