Ceramide synthase 4

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Ceramide synthase 4
Identifiers
Symbol CerS4
Alt. symbols LASS4
Entrez 79603
HUGO 23747
OMIM 615334
RefSeq NM_024552.2
UniProt Q9HA82
Other data
EC number 2.3.1.24
Locus Chr. 19 p13.3

Ceramide synthase 4 (CerS4) is an enzyme that in humans is encoded by the CERS4 gene and is one of the least studied of the ceramide synthases.

Function and distribution[edit]

CerS4 synthesizes ceramides containing C18-22 fatty acids in a fumonisin B1-independent manner.[1] It is expressed at highest levels in skin, leukocytes, heart and liver, although at much lower levels than other ceramide synthases.[2]

Clinical significance[edit]

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.[3][4] Unlike CerS1 and CerS5, CerS4 does not sensitize cells to chemotherapeutic drugs.[5]

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.[6]

CerS4 expression was also found to be elevated in the brain of an Alzheimer's disease mouse model.[7]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ Levy M, Futerman AH (2010). "Mammalian ceramide synthases.". IUBMB Life 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015. 
  6. ^ 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. 
  7. ^ 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.