Ceramide synthase 4
Identifiers
SymbolCerS4
Alt. symbolsLASS4
NCBI gene79603
HGNC23747
OMIM615334
RefSeqNM_024552.2
UniProtQ9HA82
Other data
EC number2.3.1.24
LocusChr. 19 p13.3
Search for
StructuresSwiss-model
DomainsInterPro

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 tissues and is strongly expressed in skin and muscle[1]

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.[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

  1. 1 2 Riebeling C, Allegood JC, Wang E, Merrill AH, Futerman AH (October 2003). "Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors". Journal of Biological Chemistry. 278 (44): 43452–43459. 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". Journal of Biological Chemistry. 283 (9): 5677–5684. 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): 745–752. 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". Biochemical and Biophysical Research Communications. 391 (1): 219–223. 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. hdl:10115/3350. 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. S2CID 5324040.
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