When Do Lasses (Longevity Assurance Genes) Become CerS (Ceramide Synthases)?

By Y. Pewzner‐Jung, Shifra Ben-Dor, A. Futerman. 2006

441 citations recorded by the source corpus.

Ceramide is thekey intermediate in thepathwayof sphingolipid (SL)2 biosynthesis (1) and an important intracellular signaling molecule (2, 3). Ceramide consists of a sphingoid long chain base to which a fatty acid is attached via an amide bond (Fig. 1). When the chemical composition of SLswas first determined in the 1940s (4), stearic acid (C18:0) was identified as the major fatty acid attached to the sphingoid base. Later, with the development of more sensitive techniques (5, 6), it became clear that mammalian SLs contain a wide variety of fatty acids, ranging in length from C14 to C32, that are predominantly saturated and can contain !or "-hydroxyl groups (7, 8). Within the past few years, there has been renewed interest in the functional significance of this fatty acid variability, and thisminireviewwill focus on current advances in our understanding of how the fatty acid composition of ceramide is regulated. In particular, we will discuss a recently discovered family of mammalian ceramide synthase (CerS) genes and emerging evidence that specific ceramides containing distinct fatty acids play important roles in cell growth and apoptosis.

Subfields: Biochemistry, Molecular Biology, Physiology

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Citations in the corpus

Mammalian Ceramide Synthases (2010, background): “However, the importance of the Lag1p motif in CerS activity has been demonstrated by site-directed mutagenesis (19).”
C24‐Ceramide Drives Gallbladder Cancer Progression Through Directly Targeting Phosphatidylinositol 5‐Phosphate 4‐Kinase Type‐2 Gamma to Facilitate Mammalian Target of Rapamycin Signaling Activation (2020, background): “693 palmitoyltransferase (SPTLC) and involves acylation of sphinganine with fatty acyl-CoAs to produce distinct chain lengths of ceramides that are orchestrated by six ceramide synthases (CERS1-6) with substrate specificity.(4-6) Growing evidence has established that altered ceramide metabolic pathw”
Roles of bioactive sphingolipids in cancer biology and therapeutics. (2008, background): “CerS1–6 are associated with the ER membrane and contain a crucial TRAM-Lag1p-CLN8 (TLC) domain.”
A ceramide-centric view of insulin resistance. (2012, background): “At least six genes that encode CerS have been cloned and characterized (Pewzner-Jung et al., 2006).”
Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC): attenuation of C(18)-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis. (2007, background): “Nevertheless, these data reveal that lower C18-ceramide levels, which is known to be generated by the function of hLASS1/CerS1 [46,47], in HNSCC tumors is significantly correlated with the parameters of advanced clinical disease, and support the view that C18-ceramide might play important roles in t”
CERAMIDE SYNTHASE 1 IS REGULATED BY PROTEASOMAL MEDIATED TURNOVER (2009, background): “Ceramide homeostasis in turn is dependent on the de novo synthesis of ceramide from sphinganine and acyl CoA, which is catalyzed by a family of 6 ceramide synthases [5,6].”
An overview of sphingolipid metabolism: from synthesis to breakdown (2010, background): “In mammals, six distinct (dihydro)ceramide synthases abbreviated as CerS1-6 have been identified and are encoded by six distinct genes [18], [19].”
Potentiation of cannabinoid-induced cytotoxicity in Mantle Cell Lymphoma through modulation of ceramide metabolism (2009, background): “CerS1 to CerS6 synthesize ceramides of varying chain length (2).”
Long‐chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes (2008, background): “The different species of ceramide are synthesized by a group of ceramide synthases [CerS or longevity-assurance (lass) homolog family genes], the specificity of which is characterized by the length of the fatty acid chain used as the substrate (Pewzner-Jung et al., 2006).”