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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
All gamma-secretase subunits: PS1/PS2, APH-1, PEN-2, and NCT colocalize and interact with each other in Arabidopsis thaliana protoplasts. [AtPEN-2]
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.
shedding of BCMA (show TNFRSF17 Proteins) by gamma-secretase controls plasma cells in the bone marrow and yields a potential biomarker for B-cell involvement in human autoimmune diseases
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)
The PSENEN gene is down-regulated in bovine intramuscular fibroblast cells during differentiation into adipocytes.
Presenilins, which are components of the gamma-secretase protein complex, are required for intramembranous processing of some type I transmembrane proteins, such as the Notch proteins and the beta-amyloid precursor protein. Signaling by Notch receptors mediates a wide range of developmental cell fates. Processing of the beta-amyloid precursor protein generates neurotoxic amyloid beta peptides, the major component of senile plaques associated with Alzheimer's disease. This gene encodes a protein that is required for Notch pathway signaling, and for the activity and accumulation of gamma-secretase.
, presenilin enhancer 2
, gamma-secretase subunit PEN-2
, hematopoietic stem/progenitor cells protein MDS033
, presenilin enhancer protein 2
, LRRGT00140 mRNA
, liver regeneration-related protein LRRGT00140