Ask about this productRelated genes to: LASS6 antibody
- Gene:
- CERS6 NIH gene
- Name:
- ceramide synthase 6
- Previous symbol:
- LASS6
- Synonyms:
- -
- Chromosome:
- 2q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-04-30
- Date modifiied:
- 2016-10-05
Related products to: LASS6 antibody
Related articles to: LASS6 antibody
- The tumor suppressor p53 coordinates cellular stress responses, but underlying mechanisms remain incompletely understood. We previously demonstrated that, in response to metabolic stress, C-ceramide produced by ceramide synthase 6 (CerS6) directly binds to p53, thus preventing its MDM2-mediated degradation and promoting p53 activation. Here, we investigated the structural requirements and functional consequences of ceramide binding to p53. Using a panel of p53 mutants, including naturally occurring oncogenic variants, we characterized the ceramide-binding interface of p53 and the role of amino acid substitutions within this region in metabolic stress signaling. We found that disruption of ceramide binding impaired stress-induced p53-CerS6 interaction at the endoplasmic reticulum (ER), attenuated induction of p53 target genes, and reduced cellular sensitivity to stress. Of note, certain cancer-associated p53 mutants retained ceramide binding and the ability to activate stress responses. These studies were further extended to monitoring the p53-CerS6 interaction on the ER and associated membrane aggregation using fluorescence techniques. We showed that metabolic stress-induced ER remodeling was distinct from the canonical UPR. Overall, our study defines the ceramide-binding surface within the p53 DNA-binding domain and provides novel insight into the functional role of the ceramide-p53 interaction. - Source: PubMed
Publication date: 2026/09/15
Childress Madeline SJeffries Kristen AKrupenko Sergey AKrupenko Natalia I - High-fat diets (HFDs) are a major modifiable risk factor for intestinal health. Current research focuses primarily on palmitate (C16:0); however, myristate (C14:0, rich in dairy products) has been minimally investigated. HFDs increase ceramide generation which drives endoplasmic reticulum (ER) stress; with both sphingolipids and ER stress being key contributors to intestinal biology. Whether different fatty acids uniquely impact sphingolipid metabolism and ER stress in intestinal biology has not been well defined. Human colon epithelial cells were utilized to determine the role of ceramide synthases (CerS) 5 and 6 on myristate-induced ER stress using pharmacologic inhibitors and siRNA. Intestinal epithelial cell specific CerS5 and/or CerS6 knockout mice of both sexes were fed a control, high milk-fat, or high lard-fat diet for 16 weeks. Cells and colon tissues were analyzed for lipids, mRNA, and protein. Myristate treatment increased d18:1/C14:0-ceramide and induced IRE1α-dependent ER stress. Inhibition of CerS suppressed these effects, yet knockdown of CerS5/6, the primary enzymes generating d18:1/C14:0-ceramide, unexpectedly exacerbated IRE1α activation both in vitro and in vivo, potentially due to depletion of dihydro(dh)sphingosine. Altogether, our data suggest that loss of CerS5/6 exacerbate myristate-induced intestinal ER stress in colon epithelial cells and in vivo and accumulation of dhsphingosine may provide protection. - Source: PubMed
Publication date: 2026/09/23
Doll Chelsea LGordon Mary RPadilla-Rodriguez MarcoJap EugeneBoasiako Paul AMarron Marilyn TDahl Brandon KEspinoza Keila SSeiser Drew MRen Rachel JThorne Curtis ASnider Justin MSnider Ashley J - Ceramide synthases (CerS) are key enzymes in sphingolipid metabolism that regulate fundamental cellular processes, including apoptosis, cell growth, and homeostasis. Among the six known mammalian isoforms (CerS1-CerS6), CerS5 has been particularly well studied for its involvement in the synthesis of the sphingolipid C16-ceramide. However, its expression, localization, and functional significance of CerS5 in the retina remain unclear. In the present study, we investigated the presence, distribution, and functional role of CerS5 in mouse retina using CerS5 knockout (KO) mice. We performed quantitative polymerase chain reaction, X-gal staining, and immunohistochemistry to analyze the expression and localization. Electroretinography (ERG) was employed to assess the impact of CerS5 deficiency on retinal function. Our results demonstrated that CerS5 is localized to the inner nuclear layer and ganglion cell layer, co-localizing with horizontal cells and specific subsets of amacrine and ganglion cells. The retina of CerS5 KO mice showed a reduction in overall thickness, with significant thinning observed in all retinal layers except the photoreceptor, whereas the outer plexiform layer showed increased thickness. Despite these structural alterations, ERG recordings revealed no significant changes in retinal function. These findings suggest that CerS5 contributes to the maintenance of retinal structural integrity, particularly through its presence in specific retinal cell types, whereas its loss does not markedly impair retinal function in adult mice. The observed structural alterations highlight its potential role in retinal physiology and possible implications for retinal pathophysiology, warranting further investigation into compensatory mechanisms by other ceramide synthase isoforms. - Source: PubMed
Song Soo-JinKoo Jae-HyunKim Hee-YeonPark Joo-WonPaik Sun-SookKim In-BeomShin Jung-A - To investigate clinical and peripheral blood mononuclear cells (PBMCs) transcriptomic features associated with chronic brucellosis and to test the hypothesis that lipid metabolism-related transcriptomic alterations in PBMCs may be involved in chronic disease progression. - Source: PubMed
Publication date: 2026/07/02
Wang RongNiu BinZhang XinWang YinghanTian HaiyanZhang ChenmingZhang Liaoyun - Ceramides, a diverse class of bioactive sphingolipids, play a pivotal role in cellular stress response. We have previously reported a novel mechanism by which a particular member of this class, C-ceramide, activates death pathways in cancer cells. In this mechanism, C-ceramide, generated by ceramide synthase 6 (CerS6), binds directly to the tumor suppressor p53 and protects it from MDM2-mediated degradation, thereby promoting a stress response. In the present study, we investigated the mechanism by which p53 acquires ceramide, a highly hydrophobic molecule. Using bimolecular fluorescence complementation, we show that in cells under metabolic stress, p53 is recruited to the cytoplasmic surface of the ER by CerS6, the ER resident enzyme generating C-ceramide. The direct contact between the two proteins enables the transfer of C-ceramide from CerS6 to the DNA-binding domain of p53. Domain deletion experiments and pulldown assays with purified recombinant cytoplasmic fragments of CerS6 showed that the p53 physically interacts with the two large cytoplasmic loops of CerS6, forming a complex on the surface of the ER membrane. The interaction between p53 and CerS6 strictly requires the presence of C-ceramide in the catalytic site of the enzyme. Substitution of the CerS6 lumenal loop, which defines the enzyme's acyl chain specificity, with the corresponding loop of CerS2, which generates very-long-chain ceramides, abolished the interaction with p53. Our results uncover a previously unknown process, the direct C-ceramide transfer to the p53 DNA-binding domain at the ER surface, which is a mechanism regulating activation of this tumor suppressor. The findings that this mechanism is triggered upon metabolic stress induction by specific chemotherapeutics, as well as by nutrient and growth factor deprivation, highlight it as a promising target for cancer treatment. - Source: PubMed
Publication date: 2026/07/09
Childress Madeline SJeffries Kristen AHorita David AKrupenko Sergey AKrupenko Natalia I