Ceramide synthase 4
|Ceramide synthase 4|
|Locus||Chr. 19 p13.3|
Function and distribution
CerS4 synthesizes ceramides containing C18-22 fatty acids in a fumonisin B1-independent manner. It is expressed at highest levels in skin, leukocytes, heart and liver, although at much lower levels than other ceramide synthases.
In a 2009 study of breast cancer, total ceramide synthase levels were increased in malignant tissue, and CerS4 was one of three ceramide synthases to show an increase in mRNA levels. A significant correlation was found between CerS4 and CerS2/CerS6 expression. Unlike CerS1 and CerS5, CerS4 does not sensitize cells to chemotherapeutic drugs.
CerS4 may also be involved in the control of body weight and food intake. Upon administration of leptin, a decrease in ceramide levels was observed in rat white adipose tissue, as were expression levels of a number of genes in the sphingolipid metabolic pathway, including CerS2 and CerS4.
- Riebeling C, Allegood JC, Wang E, Merrill AH, Futerman AH (2003). "Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors.". J Biol Chem 278 (44): 43452–9. doi:10.1074/jbc.M307104200. PMID 12912983.
- Laviad EL, Albee L, Pankova-Kholmyansky I, Epstein S, Park H, Merrill AH et al. (2008). "Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate.". J Biol Chem 283 (9): 5677–84. doi:10.1074/jbc.M707386200. PMID 18165233.
- Schiffmann S, Sandner J, Birod K, Wobst I, Angioni C, Ruckhäberle E et al. (2009). "Ceramide synthases and ceramide levels are increased in breast cancer tissue.". Carcinogenesis 30 (5): 745–52. doi:10.1093/carcin/bgp061. PMID 19279183.
- Erez-Roman R, Pienik R, Futerman AH (2010). "Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression.". Biochem Biophys Res Commun 391 (1): 219–23. doi:10.1016/j.bbrc.2009.11.035. PMID 19912991.
- Levy M, Futerman AH (2010). "Mammalian ceramide synthases.". IUBMB Life 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015.
- Bonzón-Kulichenko E, Schwudke D, Gallardo N, Moltó E, Fernández-Agulló T, Shevchenko A et al. (2009). "Central leptin regulates total ceramide content and sterol regulatory element binding protein-1C proteolytic maturation in rat white adipose tissue.". Endocrinology 150 (1): 169–78. doi:10.1210/en.2008-0505. PMID 18801905.
- Wang G, Silva J, Dasgupta S, Bieberich E (2008). "Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes.". Glia 56 (4): 449–56. doi:10.1002/glia.20626. PMID 18205190.