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J Biol Chem, Vol. 275, Issue 11, 7597-7603, March 17, 2000
From the Department of Biochemistry and Molecular Biology,
Uniformed Services University of the Health Sciences,
Bethesda, Maryland 20814
Serine palmitoyltransferase catalyzes the first
step of sphingolipid synthesis, condensation of serine and palmitoyl
CoA to form the long chain base 3-ketosphinganine. The
LCB1/TSC2 and LCB2/TSC1 genes encode homologous
proteins of the
Tsc3p Is an 80-Amino Acid Protein Associated with Serine
Palmitoyltransferase and Required for Optimal Enzyme Activity*
-oxoamine synthase family required for serine
palmitoyltransferase activity. The other -oxoamine synthases are
soluble homodimers, but serine palmitoyltransferase is a
membrane-associated enzyme composed of at least two subunits, Lcb1p and
Lcb2p. Here, we report the characterization of a third gene,
TSC3, required for optimal 3-ketosphinganine synthesis in
Saccharomyces cerevisiae. S. cerevisiae cells lacking the
TSC3 gene have a temperature-sensitive lethal phenotype
that is reversed by supplying 3-ketosphinganine, dihydrosphingosine, or
phytosphingosine in the growth medium. The tsc3 mutant
cells have severely reduced serine palmitoyltransferase activity. The TSC3 gene encodes a novel 80-amino acid protein with a
predominantly hydrophilic amino-terminal half and a hydrophobic
carboxyl terminus that is membrane-associated. Tsc3p
coimmunoprecipitates with Lcb1p and/or Lcb2p but does not bind as
tightly as Lcb1p and Lcb2p bind to each other. Lcb1p and Lcb2p remain
tightly associated with each other and localize to the membrane in
cells lacking Tsc3p. However, Lcb2p is unstable in cells lacking Lcb1p
and vice versa.
*
This work was supported by National Institutes of Health
Grant GM 51891 and Uniformed Services University of the Health Sciences Grant CO71DC.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biochemistry
and Molecular Biology, Uniformed Services University of the Health
Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814. Tel.:
301-295-3592; Fax: 301-295-3592; E-mail: Tdunn@usuhs.mil.
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