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Ceramide synthase 4

From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Ceramide synthase 4
Identifiers
SymbolCerS4
Alt. symbolsLASS4
NCBI gene79603
HGNC23747
OMIM615334
RefSeqNM_024552.2
UniProtQ9HA82
Other data
EC number2.3.1.24
LocusChr. 19p13.3
Search for
StructuresSwiss-model
DomainsInterPro

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

Function and distribution

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CerS4 synthesizesceramides containing C18-22fatty acids in afumonisin B1-independent manner.[1] It is expressed at highest levels inskin,leukocytes,heart andliver, although at much lower levels than other ceramide synthases.[2]

Tissue and cellular distribution

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CerS4 (TRH1) mRNA was found in all tissues and is strongly expressed in skin and muscle[1]

Clinical significance

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In a 2009 study ofbreast cancer, total ceramide synthase levels were increased in malignant tissue, and CerS4 was one of three ceramide synthases to show an increase inmRNA levels. A significant correlation was found between CerS4 andCerS2/CerS6 expression.[3][4] UnlikeCerS1 andCerS5, CerS4 does not sensitize cells to chemotherapeutic drugs.[5]

CerS4 may also be involved in the control ofbody weight andfood intake. Upon administration ofleptin, a decrease in ceramide levels was observed inratwhite adipose tissue, as were expression levels of a number of genes in thesphingolipid metabolic pathway, including CerS2 and CerS4.[6]

CerS4 expression was also found to be elevated in thebrain of anAlzheimer's diseasemouse model.[7]

References

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  1. ^abRiebeling 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.Bibcode:2010BBRC..391..219E.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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