1. Function

2. As a glioblastoma drug target

3. References

4. External links

5. Further reading

The ASAH1 gene encodes in humans the acid ceramidase enzyme.^[1][2][3]

Function

This gene encodes a heterodimeric protein consisting of a nonglycosylated alpha subunit and a glycosylated beta subunit that is cleaved to the mature enzyme posttranslationally. The encoded protein catalyzes the synthesis and degradation of ceramide into sphingosine and fatty acid. Mutations in this gene have been associated with a lysosomal storage disorder known as Farber disease and, recently, with a rare neurodegenerative condition known as spinal muscular atrophy with progressive myoclonic epilepsy.^[4] Two transcript variants encoding distinct isoforms have been identified for this gene.^[3] In melanocytic cells ASAH1 gene expression may be regulated by MITF.^[5]

As a glioblastoma drug target

ASAH1 expression is upregulated following radiation, suggesting it plays a role in conferring radioresistance to glioblastoma and in the development of recurrent glioblastoma.^[6] Inhibiting the activity of ASAH1 with carmofur, a drug that has been approved for clinical treatment of colorectal cancers in several countries, leads to substantial cell deaths and as a result has been proposed as a drug target in the treatment of glioblastoma.^[7] It has also been suggested to be a novel drug target against pediatric brain tumors as well.^[8]

References

External links

• {{UCSC gene info|ASAH1}}

Further reading

• {{cite journal | vauthors = Perry DK, Hannun YA | title = The role of ceramide in cell signaling | journal = Biochimica et Biophysica Acta | volume = 1436 | issue = 1–2 | pages = 233–43 | date = December 1998 | pmid = 9838138 | doi = 10.1016/S0005-2760(98)00145-3 }}
• {{cite journal | vauthors = Bernardo K, Hurwitz R, Zenk T, Desnick RJ, Ferlinz K, Schuchman EH, Sandhoff K | title = Purification, characterization, and biosynthesis of human acid ceramidase | journal = The Journal of Biological Chemistry | volume = 270 | issue = 19 | pages = 11098–102 | date = May 1995 | pmid = 7744740 | doi = 10.1074/jbc.270.19.11098 }}
• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
• {{cite journal | vauthors = Seelan RS, Qian C, Yokomizo A, Bostwick DG, Smith DI, Liu W | title = Human acid ceramidase is overexpressed but not mutated in prostate cancer | journal = Genes, Chromosomes & Cancer | volume = 29 | issue = 2 | pages = 137–46 | date = October 2000 | pmid = 10959093 | doi = 10.1002/1098-2264(2000)9999:9999<::AID-GCC1018>3.0.CO;2-E }}
• {{cite journal | vauthors = Strelow A, Bernardo K, Adam-Klages S, Linke T, Sandhoff K, Krönke M, Adam D | title = Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death | journal = The Journal of Experimental Medicine | volume = 192 | issue = 5 | pages = 601–12 | date = September 2000 | pmid = 10974027 | pmc = 2193270 | doi = 10.1084/jem.192.5.601 }}
• {{cite journal | vauthors = Bär J, Linke T, Ferlinz K, Neumann U, Schuchman EH, Sandhoff K | title = Molecular analysis of acid ceramidase deficiency in patients with Farber disease | journal = Human Mutation | volume = 17 | issue = 3 | pages = 199–209 | date = March 2001 | pmid = 11241842 | doi = 10.1002/humu.5 }}
• {{cite journal | vauthors = Ferlinz K, Kopal G, Bernardo K, Linke T, Bar J, Breiden B, Neumann U, Lang F, Schuchman EH, Sandhoff K | title = Human acid ceramidase: processing, glycosylation, and lysosomal targeting | journal = The Journal of Biological Chemistry | volume = 276 | issue = 38 | pages = 35352–60 | date = September 2001 | pmid = 11451951 | doi = 10.1074/jbc.M103066200 }}
• {{cite journal | vauthors = Muramatsu T, Sakai N, Yanagihara I, Yamada M, Nishigaki T, Kokubu C, Tsukamoto H, Ito M, Inui K | title = Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease | journal = Journal of Inherited Metabolic Disease | volume = 25 | issue = 7 | pages = 585–92 | date = November 2002 | pmid = 12638942 | doi = 10.1023/A:1022047408477 }}
• {{cite journal | vauthors = Zhang H, Li XJ, Martin DB, Aebersold R | title = Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry | journal = Nature Biotechnology | volume = 21 | issue = 6 | pages = 660–6 | date = June 2003 | pmid = 12754519 | doi = 10.1038/nbt827 }}
• {{cite journal | vauthors = Okino N, He X, Gatt S, Sandhoff K, Ito M, Schuchman EH | title = The reverse activity of human acid ceramidase | journal = The Journal of Biological Chemistry | volume = 278 | issue = 32 | pages = 29948–53 | date = August 2003 | pmid = 12764132 | doi = 10.1074/jbc.M303310200 }}
• {{cite journal | vauthors = He X, Okino N, Dhami R, Dagan A, Gatt S, Schulze H, Sandhoff K, Schuchman EH | title = Purification and characterization of recombinant, human acid ceramidase. Catalytic reactions and interactions with acid sphingomyelinase | journal = The Journal of Biological Chemistry | volume = 278 | issue = 35 | pages = 32978–86 | date = August 2003 | pmid = 12815059 | doi = 10.1074/jbc.M301936200 }}
• {{cite journal | vauthors = Hara S, Nakashima S, Kiyono T, Sawada M, Yoshimura S, Iwama T, Banno Y, Shinoda J, Sakai N | title = p53-Independent ceramide formation in human glioma cells during gamma-radiation-induced apoptosis | journal = Cell Death and Differentiation | volume = 11 | issue = 8 | pages = 853–61 | date = August 2004 | pmid = 15088070 | doi = 10.1038/sj.cdd.4401428 }}
• {{cite journal | vauthors = Lewandrowski U, Moebius J, Walter U, Sickmann A | title = Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach | journal = Molecular & Cellular Proteomics | volume = 5 | issue = 2 | pages = 226–33 | date = February 2006 | pmid = 16263699 | doi = 10.1074/mcp.M500324-MCP200 }}

• Algebraic extension of a field
• Algebraic form
• Algebraic forms
• Algebraic Forms
• Algebraic function
• Algebraic function field
• Algebraic functions
• Algebraic Geometry
• Algebraic geometry
• Algebraic geometry and analytic geometry
• Algebraic graph theory
• Algebraic group
• Algebraic groups
• Algebraic independence
• Algebraic integer
• Algebraic integers
• Algebraic invariant
• Algebraic K-theory
• Algebraic multiplicity
• Algebraic normal form
• Algebraic notation
• Algebraic notation (chess)
• Algebraic number
• Algebraic numbers
• Algebraic number theory