Ceramide synthase 4

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.

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

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. 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. 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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