Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.16 (
calcineurin
)
17,112
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glycogen-targeting PP1 (
protein phosphatase
1) subunit G(L) (coded for by the PPP1R3B gene) is expressed in human, but not rodent, skeletal muscle. Its effects on muscle glycogen metabolism are unknown. We show that G(L) mRNA levels in primary cultured human myotubes are similar to those in freshly excised muscle, unlike subunits G(M) (gene PPP1R3A) or PTG (protein targeting to glycogen; gene
PPP1R3C
), which decrease strikingly. In cultured myotubes, expression of the genes coding for G(L), G(M) and PTG is not regulated by glucose or insulin. Overexpression of G(L) activates myotube GS (glycogen synthase), glycogenesis in glucose-replete and -depleted cells and glycogen accumulation. Compared with overexpressed G(M), G(L) has a more potent activating effect on glycogenesis, while marked enhancement of their combined action is only observed in glucose-replete cells. G(L) does not affect GP (glycogen phosphorylase) activity, while co-overexpression with muscle GP impairs G(L) activation of GS in glucose-replete cells. G(L) enhances long-term glycogenesis additively to glucose depletion and insulin, although G(L) does not change the phosphorylation of GSK3 (GS kinase 3) on Ser9 or its upstream regulator kinase Akt/protein kinase B on Ser473, nor its response to insulin. In conclusion, in cultured human myotubes, the G(L) gene is expressed as in muscle tissue and is unresponsive to glucose or insulin, as are G(M) and PTG genes. G(L) activates GS regardless of glucose, does not regulate GP and stimulates glycogenesis in combination with insulin and glucose depletion.
...
PMID:Expression and glycogenic effect of glycogen-targeting protein phosphatase 1 regulatory subunit GL in cultured human muscle. 1755 3
Molecular mechanisms responsible for gonadotrophic control of ovarian follicle development and ovulation have not been fully delineated. In this study, prepubertal female rabbits were subjected to a combined PMSG/hCG treatment for the induction of follicle maturation and ovulation. Ovaries of 6 does at different time points during gonadotrophic stimulation were collected for histomorphological examination and genome-wide analysis of miRNA and mRNA transcriptomes, and the plasma were separated for detecting melatonin (MT), prostaglandin E
2
(PGE
2
), estradiol (E
2
), and progesterone (P
4
) levels. The results suggested that PMSG promoted the development of the reproductive tract by decreasing plasma levels of E
2
and slightly increasing those of MT and PGE
2
and that hCG induced ovulation and corpus luteum formation by significantly increasing MT, PGE
2
, and P
4
levels. At the transcriptomic level, a total of 1,122 differentially expressed genes (DEGs) and 12 DE miRNAs were identified using three-group comparisons. Meanwhile, pairwise comparisons revealed that 279 and 103 genes as well as 36 and 20 miRNAs were up- and down-regulated during PMSG-stimulated follicle development while 11 and 5 genes as well as 33 and 16 miRNAs were up- and down-regulated during hCG-induced luteinization. KEGG enrichment analysis of the DEGs derived from both three-group- and two-group comparisons as well as the predicted target genes of DE miRNAs highlighted the crucial roles of pathways involving tissue remodeling, energy metabolism, and regulation of cellular functions in mediating gonadotrophin-induced follicle maturation. Specifically, 3 genes including the matrix metallopeptidase 13 (
MMP13
),
protein phosphatase
1 regulatory subunit 3C (
PPP1R3C
), and solute carrier family 2 member 12 (
SLC2A12
), together with 2 miRNAs including the miR-205-1 and miR-34c, were predicted to be the promising downstream targets of both PMSG and hCG. Significantly, the miRNA-mRNA interaction pairs containing top 10 up- and down-regulated mRNAs/miRNAs upon PMSG/hCG stimulation were established, and so were those involved in the PI3K-Akt, ECM-receptor interaction, and focal adhesion pathways during PMSG-induced follicle maturation. Finally, qRT-PCR analysis confirmed the results from RNA-Seq and Small RNA-Seq. Our work may contribute to a better understanding of the regulatory mechanisms of gonadotrophins on ovarian follicle development and ovulation.
...
PMID:Integrated Analysis of mRNA and miRNA Expression Profiles in the Ovary of
Oryctolagus cuniculus
in Response to Gonadotrophic Stimulation. 3173 80
Mammalian glycogen chain lengths are subject to complex regulation, including by seven proteins (
protein phosphatase-1
regulatory subunit 3, PPP1R3A through PPP1R3G) that target
protein phosphatase-1
(PP1) to glycogen to activate the glycogen chain-elongating enzyme glycogen synthase and inactivate the chain-shortening glycogen phosphorylase. Lafora disease is a fatal neurodegenerative epilepsy caused by aggregates of long-chained, and as a result insoluble, glycogen, termed Lafora bodies (LBs). We previously eliminated
PPP1R3C
from a Lafora disease mouse model and studied the effect on LB formation. In the present work, we eliminate and study the effect of absent PPP1R3D. In the interim, brain cell type levels of all PPP1R3 genes have been published, and brain cell type localization of LBs clarified. Integrating these data we find that
PPP1R3C
is the major isoform in most tissues including brain. In the brain,
PPP1R3C
is expressed at 15-fold higher levels than PPP1R3D in astrocytes, the cell type where most LBs form.
PPP1R3C
deficiency eliminates ~90% of brain LBs. PPP1R3D is quantitatively a minor isoform, but possesses unique MAPK, CaMK2 and 14-3-3 binding domains and appears to have an important functional niche in murine neurons and cardiomyocytes. In neurons, it is expressed equally to
PPP1R3C
, and its deficiency eliminates ~50% of neuronal LBs. In heart, it is expressed at 25% of
PPP1R3C
where its deficiency eliminates ~90% of LBs. This work studies the role of a second (PPP1R3D) of seven PP1 subunits that regulate the structure of glycogen, toward better understanding of brain glycogen metabolism generally, and in Lafora disease.
...
PMID:Ppp1r3d deficiency preferentially inhibits neuronal and cardiac Lafora body formation in a mouse model of the fatal epilepsy Lafora disease. 3289 47
Background:
Renal cell carcinoma (RCC) is one of the most common and malignant tumors in the urinary system. This article set out with the aim of investigating the mechanism and clinical significance of
miR-4461
in the RCC progression.
Materials and Methods:
Twenty-eight (28) paired RCC tissue samples and adjacent nontumor tissue samples, as well as RCC cell lines were used to measure the expression of
miR-4461
and
protein phosphatase
1 regulatory subunit 3C (
PPP1R3C
) transcript by real-time quantitative PCR. The target relationship between
miR-4461
and
PPP1R3C
was predicted by TargetScan and further verified by dual-luciferase reporter gene assay and RNA pull-down assay. Cell Counting Kit-8 (CCK-8) assay and BrdU ELISA assay were implemented to measure RCC cell viability and proliferation. In addition, caspase-3 activity assay and cell adhesion assay were implemented to measure RCC cell apoptosis and adhesion.
Results:
MiR-4461
was lowly expressed both in RCC tissues and cells, while upregulated
PPP1R3C
was tested in RCC tissues and cells. In addition,
miR-4461
was validated to directly target
PPP1R3C
, thereby negatively regulating
PPP1R3C
. Particularly,
miR-4461
exerted a clear inhibitory effect on the malignant phenotypes of RCC cells by binding and inhibiting
PPP1R3C
.
Conclusion:
MiR-4461
, which served as a tumor suppressor, inhibited RCC progression by targeting and downregulating
PPP1R3C
.
...
PMID:
MiR-4461
Inhibits Tumorigenesis of Renal Cell Carcinoma by Targeting
PPP1R3C
. 3291 48
