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APP (show APP Proteins) substrate occupancy of these three pockets of gamma-secretase occurs after initial substrate binding but precedes catalysis, suggesting a conformational change in substrate may be required for cleavage.
PSENEN mutations can indeed cause a comanifestation of Dowling-Degos disease and acne inversa (AI) that is likely triggered by predisposing factors for AI.
zinc, copper inhibited Abeta (show APP Proteins) production by directly targeting the subunits presenilin and nicastrin (show NCSTN Proteins) in the gamma-secretase complex
PSENEN may play a crucial role in the progression of atopic dermatitis by participating in the Notch (show NOTCH1 Proteins) signaling pathway.
Remarkably, PEN-2 was identified besides nicastrin (show NCSTN Proteins) as additional substrate-binding subunit.
TRPC6 (show TRPC6 Proteins) specifically interacts with APP (show APP Proteins) leading to inhibition of its cleavage by gamma-secretase and reduction in Abeta (show APP Proteins) production.
secondary mutations in presenilin 1 (show PSEN1 Proteins) alone activated the gamma-secretase activity.
Data indicate that familial Alzheimer's disease (FAD (show BRCA2 Proteins)) and control brain samples had similar overall gamma-secretase activity levels, and therefore, loss of overall (endopeptidase) gamma-secretase function cannot be an essential part of the pathogenic mechanism.
We for the first time identify PEN-2 as the causative gene of familial comedones.
The first hydrophobic domain of Pen-2 forms a structure similar to a reentrant loop while the second hydrophobic domain spans the lipid bilayer.
The PSENEN gene is down-regulated in bovine intramuscular fibroblast cells during differentiation into adipocytes.
Using knockout cell lines in combination with siRNA and immunoprecipitation approaches, our data clearly demonstrated that the Pen-2 and PS1 (show PSEN1 Proteins) are sufficient to form a functionally active gamma-secretase that is capable of catalyzing the processing of Notch (show NOTCH1 Proteins). This finding strongly suggests that Pen-2 is the most crucial component in gamma-secretase complex in addition to presenilin that functions as the catalytic subunit.
Cleavage of the Interleukin-11 receptor (show IL11RA Proteins) induces processing of its C-terminal fragments by the gamma-secretase and the proteasome.
the G206D mutation reduced presenilin-1 (show PSEN1 Proteins)-presenilin enhancer 2 interaction, but did not abolish gamma-secretase formation and presenilin-1 (show PSEN1 Proteins) endoproteolysis
Data show that the expression level of presenilin enhancer-2 (Pen-2) is relatively high in central nervous system at the early stages of postnatal development, but declines, gradually in adult mice.
rather than solely being a catalyst for gamma-secretase endoproteolysis, Pen-2 may also stabilize the complex prior to PS1 (show PSEN1 Proteins) endoproteolysis, allowing time for full assembly and proper trafficking.
Pen-2, as well as nicastrin and Aph-1alpha, is dispensable for presenilin endoproteolysis
Nct (show NCSTN Proteins) has a critical role in the stability and proper intracellular trafficking of other components of the PS1 (show PSEN1 Proteins)/ gamma-secretase complex but not in maintaining the association of PEN-2, APH-1, and full-length PS1 (show PSEN1 Proteins)
APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex.
presenilin, nicastrin (show NCSTN Proteins), APH-1, and PEN-2, are present and enriched on phagosome membranes from both murine macrophages and Drosophila S2 phagocytes
The protein encoded by this gene belongs to the small nuclear ribonucleoprotein core protein family. It is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis.
gamma-secretase subunit PEN-2
, hematopoietic stem/progenitor cells protein MDS033
, presenilin enhancer protein 2
, presenilin enhancer 2
, small nuclear ribonucleoprotein Sm D3
, snRNP core protein D3
, LRRGT00140 mRNA
, liver regeneration-related protein LRRGT00140
, Presenilin enhancer protein 2 homolog
, presenilin enhancer 2 homolog
, presenilin enhancer protein 2 homolog