Ceramide synthase 4: Difference between revisions
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==Function and distribution== | ==Function and distribution== | ||
CerS4 synthesizes [[ceramides]] containing C18-22 [[fatty acid]]s in a [[fumonisin B1]]-independent manner.<ref name= | CerS4 synthesizes [[ceramides]] containing C18-22 [[fatty acid]]s in a [[fumonisin B1]]-independent manner.<ref name=pmid12912983>{{cite journal|vauthors=Riebeling C, Allegood JC, Wang E, Merrill AH, Futerman AH | title=Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors | journal=Journal of Biological Chemistry | year= October 2003 | volume= 278 | issue= 44 | pages= 43452–43459 | doi=10.1074/jbc.M307104200 | pmc= | pmid=12912983}}</ref> It is expressed at highest levels in [[skin]], [[leukocyte]]s, [[heart]] and [[liver]], although at much lower levels than other ceramide synthases.<ref name="pmid18165233">{{cite journal |vauthors=Laviad EL, Albee L, Pankova-Kholmyansky I, Epstein S, Park H, Merrill AH, etal | title=Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate | journal=Journal of Biological Chemistry | year= 2008 | volume= 283 | issue= 9 | pages= 5677–5684 | doi=10.1074/jbc.M707386200 | pmc= | pmid=18165233}}</ref> | ||
== Tissue and cellular distribution == | == Tissue and cellular distribution == | ||
CerS4 (TRH1) mRNA was found in all | CerS4 (TRH1) mRNA was found in all tissues and is strongly expressed in skin and muscle<ref name=pmid12912983/> | ||
==Clinical significance== | ==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.<ref name="pmid19279183">{{cite journal |vauthors=Schiffmann S, Sandner J, Birod K, Wobst I, Angioni C, Ruckhäberle E, etal | title=Ceramide synthases and ceramide levels are increased in breast cancer tissue | 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 (gene)|CerS6]] expression.<ref name="pmid19279183">{{cite journal |vauthors=Schiffmann S, Sandner J, Birod K, Wobst I, Angioni C, Ruckhäberle E, etal | title=Ceramide synthases and ceramide levels are increased in breast cancer tissue | journal=Carcinogenesis | year= 2009 | volume= 30 | issue= 5 | pages= 745–752 | doi=10.1093/carcin/bgp061 | pmc= | pmid=19279183}}</ref><ref name="pmid19912991">{{cite journal|vauthors=Erez-Roman R, Pienik R, Futerman AH | title=Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression | journal=Biochemical and Biophysical Research Communications | year= 2010 | volume= 391 | issue= 1 | pages= 219–223 | doi=10.1016/j.bbrc.2009.11.035 | pmc= | pmid=19912991 }}</ref> Unlike [[CerS1]] and [[CerS5]], CerS4 does not sensitize cells to chemotherapeutic drugs.<ref name="pmid20222015">{{cite journal|vauthors=Levy M, Futerman AH | title=Mammalian ceramide synthases | journal=IUBMB Life | year= 2010 | volume= 62 | issue= 5 | pages= 347–56 | pmid=20222015 | doi=10.1002/iub.319 | pmc=2858252 }}</ref> | ||
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 [[lab rat|rat]] [[white adipose tissue]], as were expression levels of a number of genes in the [[sphingolipid]] metabolic pathway, including CerS2 and CerS4.<ref name="pmid18801905">{{cite journal |vauthors=Bonzón-Kulichenko E, Schwudke D, Gallardo N, Moltó E, Fernández-Agulló T, Shevchenko A, etal | title=Central leptin regulates total ceramide content and sterol regulatory element binding protein-1C proteolytic maturation in rat white adipose tissue | 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 [[lab rat|rat]] [[white adipose tissue]], as were expression levels of a number of genes in the [[sphingolipid]] metabolic pathway, including CerS2 and CerS4.<ref name="pmid18801905">{{cite journal |vauthors=Bonzón-Kulichenko E, Schwudke D, Gallardo N, Moltó E, Fernández-Agulló T, Shevchenko A, etal | title=Central leptin regulates total ceramide content and sterol regulatory element binding protein-1C proteolytic maturation in rat white adipose tissue | journal=Endocrinology | year= 2009 | volume= 150 | issue= 1 | pages= 169–78 | doi=10.1210/en.2008-0505 | pmc= | pmid=18801905}}</ref> | ||
CerS4 expression was also found to be elevated in the [[brain]] of an [[Alzheimer's disease]] [[mouse model]].<ref name="pmid18205190">{{cite journal|vauthors=Wang G, Silva J, Dasgupta S, Bieberich E | title=Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes | CerS4 expression was also found to be elevated in the [[brain]] of an [[Alzheimer's disease]] [[mouse model]].<ref name="pmid18205190">{{cite journal|vauthors=Wang G, Silva J, Dasgupta S, Bieberich E | title=Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes | journal=Glia | year= 2008 | volume= 56 | issue= 4 | pages= 449–56 | doi=10.1002/glia.20626 | pmc= | pmid=18205190 }}</ref> | ||
==References== | ==References== | ||
Latest revision as of 18:08, 9 December 2018
| 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 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
- ↑ 1.0 1.1 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Levy M, Futerman AH (2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015.
- ↑ 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.
- ↑ 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.