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General Comment |
Spermidine/spermine N(1)-acetyltransferase (SPD/SPM acetyltransferase) is a rate-limiting enzyme in the catabolic
pathway of polyamine metabolism. It catalyzes the N(1)-acetylation of spermidine and spermine and, by the successive
activity of polyamine oxidase, spermine can be converted to spermidine and spermidine to putrescine.
NCBI Summary:
The protein encoded by this gene belongs to the acetyltransferase family, and is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the acetylation of spermidine and spermine, and is involved in the regulation of the intracellular concentration of polyamines and their transport out of cells. Defects in this gene are associated with keratosis follicularis spinulosa decalvans (KFSD). Alternatively spliced transcripts have been found for this gene.[provided by RefSeq, Sep 2009]
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Comment |
Min SH, et al reported altered levels of growth-related and novel gene transcripts in reproductive
and other tissues of female mice over-expressing spermidine/spermine
N1-acetyltransferase (SSAT).
Over-expression of SSAT (polyamine catabolic enzyme) in female mice results in impaired
ovarian folliculogenesis and uterine hypoplasia. To identify the molecular basis for this, the gene
expression profiles in uterus and ovary and for comparison, liver and kidney, from
non-transgenic (NT) and SSAT transgenic (ST) mice were compared. The mRNA abundance for
lipoprotein lipase and glyceraldehyde-3-phosphate dehydrogenase was elevated in all four ST
(>NT) tissues. SSAT over-expression was associated with increased
levels of IGF-binding protein-2 (IGFBP-2) in the uterus and ovary, and a reduction in IGFBP-3
mRNA levels in the uterus. Exogenous spermidine and spermine elevated endogenous IGFBP-2
and SSAT mRNA abundance, whereas, putrescine stimulated IGFBP-2 mRNA abundance and
transfected IGFBP-2 gene promoter activity in human (Hec-1-A) uterine cells. Sp1 and BTEB1
mRNAs that encode transcription factors for the IGFBP-2 gene also were induced in some ST
tissues. The data suggest that SSAT and polyamines are important for the control of molecular
pathways underlying reproductive tract tissue growth, phenotype and function.
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Comment |
Gene expression profiling of upregulated mRNAs in granulosa cells of bovine ovulatory follicles following stimulation with hCG. Lussier JG et al. (2017) Ovulation and luteinization of follicles are complex biological processes initiated by the preovulatory luteinizing hormone surge. The objective of this study was to identify genes that are differentially expressed in bovine granulosa cells (GC) of ovulatory follicles. Granulosa cells were collected during the first follicular wave of the bovine estrous cycle from dominant follicles (DF) and from ovulatory follicles (OF) obtained 24 h following injection of human chorionic gonadotropin (hCG). A granulosa cell subtracted cDNA library (OF-DF) was generated using suppression subtractive hybridization and screened. Detection of genes known to be upregulated in bovine GC during ovulation, such as ADAMTS1, CAV1, EGR1, MMP1, PLAT, PLA2G4A, PTGES, PTGS2, RGS2, TIMP1, TNFAIP6 and VNN2 validated the physiological model and analytical techniques used. For a subset of genes that were identified for the first time, gene expression profiles were further compared by semiquantitative RT-PCR in follicles obtained at different developmental stages. Results confirmed an induction or upregulation of the respective mRNAs in GC of OF 24 h after hCG-injection compared with those of DF for the following genes: ADAMTS9, ARAF, CAPN2, CRISPLD2, FKBP5, GFPT2, KIT, KITLG, L3MBLT3, MRO, NUDT10, NUDT11, P4HA3, POSTN, PSAP, RBP1, SAT1, SDC4, TIMP2, TNC and USP53. In bovine GC, CRISPLD2 and POSTN mRNA were found as full-length transcript whereas L3MBLT3 mRNA was alternatively spliced resulting in a truncated protein missing the carboxy-terminal end amino acids, (774)KNSHNEL(780). Conversely, L3MBLT3 is expressed as a full-length mRNA in a bovine endometrial cell line. The (774)KNSHNEL(780) sequence is well conserved in all mammalian species and follows a SAM domain known to confer protein/protein interactions, which suggest a key function for these amino acids in the epigenetic control of gene expression. We conclude that we have identified novel genes that are upregulated by hCG in bovine GC of OF, thereby providing novel insight into peri-ovulatory regulation of genes that contribute to ovulation and/or luteinization processes.//////////////////
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Mutations |
1 mutations
Species: mouse
Mutation name: None
type: targeted overexpression
fertility: infertile - ovarian defect
Comment: Pietila M, et al 1997 reported that activation of polyamine catabolism profoundly alters tissue polyamine
pools and affects hair growth and female fertility in transgenic mice
overexpressing spermidine/spermine N1-acetyltransferase.
The authors have generated a transgenic mouse line that overexpresses the rate-controlling enzyme of polyamine catabolism,
spermidine/spermine N1-acetyltransferase. Tissues of these mice showed markedly distorted polyamine pools, which in
most cases were characterized by the appearance of N1-acetylspermidine, not normally found in mouse tissues, a
massive accumulation of putrescine, and decreases in spermidine and/or spermine pools. Female members of the transgenic
line were found to be infertile apparently due to ovarian hypofunction and hypoplastic uteri. The findings demonstrate
the utility of spermidine/spermine N1-acetyltransferase overexpression as an effective means for genetically modulating
total tissue polyamine pools in transgenic animals and examining the developmental and oncogenic consequences.
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