Disease relevance of Scd2

• These genes included the rat homologues of human galectin-7 gene, the human/mouse melanoma inhibitory activity/bovine chondrocyte-derived retinoic acid sensitive protein gene, the mouse stearoyl-CoA desaturase-2 gene, and the mouse endo B cytokeratin/human cytokeratin-18 gene [1].

High impact information on Scd2

• The liver, skin, and plasma triglyceride contents are decreased in the neonates but are not altered in the adult Scd2-/- mice [2].
• SCD2-deficient (Scd2-/-) neonatal mice have a skin permeability barrier defect and a specific repartitioning of linoleic acid from epidermal acylceramide species into phospholipids [2].
• Stearoyl-CoA desaturase-2 gene expression is required for lipid synthesis during early skin and liver development [2].
• Taken together these results suggest that the PRE site and binding protein may regulate transcription of SCD2 and possibly other adipocyte genes by inhibiting their transcription in preadipocytes [3].
• Transfection experiments with chimeric SCD2 promoter-chloramphenicol acetyltransferase (CAT) reporter gene constructs revealed a preadipocyte repressor element (PRE) capable of repressing transcription of the reporter gene in preadipocytes but not in adipocytes [3].

Biological context of Scd2

• A cluster of stearoyl CoA desaturase genes, Scd1 and Scd2, on mouse chromosome 19 [4].
• Additional studies demonstrate that maximal transcriptional repression of SCD2 reporter genes in response to an exogenous polyunsaturated fatty acid is dependent upon the SRE and the adjacent CCAAT motif [5].
• Mutation of either of these putative NF-Y binding sites attenuates the transcriptional activation of SCD1 or SCD2 promoter-reporter genes in response to cellular sterol deprivation [5].
• Two conserved cis elements (5'-CCAAT-3') lie 5 and 48 base pairs 3' of the novel SREs in the promoters of both the SCD1 and SCD2 murine genes [5].

Anatomical context of Scd2

• We previously identified stearoyl-CoA desaturase 2 (SCD2) as a new member of the family of genes that are transcriptionally regulated in response to changing levels of nuclear sterol regulatory element binding proteins (SREBPs) or adipocyte determination and differentiation factor 1 (ADD1) [5].
• DNase I protection and gel retardation analyses were used to localize the PRE site between nucleotides -435 and -410 of the SCD2 promoter and to identify a nuclear PRE binding protein present at high levels in preadipocytes and HeLa cells but lacking or inactive in adipocytes [3].
• The finding that the endogenous SCD2 mRNA levels were induced when wild-type Chinese hamster ovary fibroblasts were incubated in sterol-deficient medium is consistent with a role for SREBP in regulating transcription of the gene [6].

Associations of Scd2 with chemical compounds

• A novel sterol regulatory element (SRE) (5'-AGCAGATTGTG-3') identified in the proximal promoter of the mouse SCD2 gene is required for induction of SCD2 promoter-reporter genes in response to cellular sterol depletion (Tabor, D. E., Kim, J. B., Spiegelman, B. M., and Edwards, P. A. (1998) J. Biol. Chem. 273, 22052-22058) [5].
• By using the protein synthesis inhibitor, cycloheximide, we also show that the 20:4-mediated regulatory effects upon SCD2 or c-fos are completely independent of new protein synthesis [7].
• Moreover, oxidized metabolites of 20:4 (15-HPETE and 15-HETE) failed to diminish SCD2 mRNA accumulation whereas 20:4 itself was effective in completely suppressing SCD2 gene expression [7].
• During the time period when stearoyl-CoA desaturase 2 transcription and unsaturated fatty acid synthesis increased (6-12 h), there was only a minimal depletion (approximately 2%) of the total phospholipid arachidonic acid-content [8].
• Induction of stearoyl-CoA desaturase 2 gene expression correlates with fatty acid changes in phosphatidylcholine [8].

Other interactions of Scd2

• Previously, two members of this gene family, namely, Scd1 and Scd2, have been reported [9].
• Transcriptional activation of the stearoyl-CoA desaturase 2 gene by sterol regulatory element-binding protein/adipocyte determination and differentiation factor 1 [6].
• The inhibition of adipogenesis caused by SCD2 depletion was associated with a decrease in peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA and protein, whereas in mature adipocytes loss of SCD2 diminished PPARgamma protein levels, with little change in mRNA levels [10].

References