Ceramide synthase 4

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

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]

Tissue and cellular distribution

CerS4 (TRH1) mRNA was found in all tisues and is strongly expressed in skin and muscle.[3]

Clinical significance

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.[4][5] Unlike CerS1 and CerS5, CerS4 does not sensitize cells to chemotherapeutic drugs.[6]

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.[7]

CerS4 expression was also found to be elevated in the brain of an Alzheimer's disease mouse model.[8]

References

  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. ↑ Riebeling C, Allegood JC, Wang E, Merrill AH Jr, Futerman AH (Oct 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ Levy M, Futerman AH (2010). "Mammalian ceramide synthases.". IUBMB Life 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015.
  7. ↑ 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.
  8. ↑ 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.
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