Ceramide synthase 1

Ceramide synthase 1 also known as LAG1 longevity assurance homolog 1 is an is_associated_with::enzyme that in humans is encoded by the CERS1 is_associated_with::gene.

Function
This gene encodes a member of the is_associated_with::bone morphogenetic protein (BMP) family and the is_associated_with::TGF-beta superfamily. This group of proteins is characterized by a polybasic proteolytic processing site that is cleaved to produce a mature protein containing seven conserved cysteine residues. Members of this family are regulators of cell growth and differentiation in both embryonic and adult tissues. Studies in yeast suggest that the encoded protein is involved in aging. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1.

Ceramide synthase 1 (CerS1) is a is_associated_with::ceramide synthase that catalyzes the synthesis of C18 is_associated_with::ceramide in a is_associated_with::fumonisin B1-independent manner, and it primarily expressed in the is_associated_with::brain. It can also be found in low levels in is_associated_with::skeletal muscle and the is_associated_with::testis. Within the cell, CerS1 is located in the is_associated_with::endoplasmic reticulum (ER) and is_associated_with::golgi apparatus membrane. CerS1 has two is_associated_with::isoforms and isoform 1 may recycle from the golgi to the ER.

Within the brain, CerS1 is the primary CerS expressed in most is_associated_with::neurons. In is_associated_with::white matter, it can only be found in low levels.

In a recent experiment performed in mice in 2012, ablation of neuronal CerS1 decreased levels of is_associated_with::sphingolipids, hexosylceramides, and is_associated_with::sphingomyelin. Although the brains in these mice appeared to develop normally, researchers observed is_associated_with::atrophy of the is_associated_with::cerebellum, and is_associated_with::Purkinje neurons appeared to degenerate. is_associated_with::Granule cells also showed a 6 times increased rate of is_associated_with::apoptosis. Behaviorally, the mice expressed motor and neurophysiological impairment.

Structure
Unlike other mammalian ceramides, CerS1 does not appear to have a Hox-like domain. It is functionally and structurally distinct from other CerS and is found in an entirely different branch of the is_associated_with::phylogenetic tree.

Clinical significance
On application of various stresses, CerS1 turns over rapidly by is_associated_with::ubiquitination and proteasomal degradation, suggesting that is has a short half life.

It has been suggested that CerS1 is involved with the regulation of the growth of head and neck squamous cell carcinoma (HNSCC), based on the information that C18 ceramide levels are lower in HNSCC tissues than in normal tissue. CerS1, in particular amongst other CerS, has also been shown to sensitize cells to is_associated_with::chemotherapeutic drugs, such as is_associated_with::cisplatin, is_associated_with::carboplatin, is_associated_with::doxorubicin, and is_associated_with::vincristine.