TNIP2 inhibits amyloidogenesis by regulating the 3'UTR of BACE1: An in vitro study.
TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-?B signaling and inhibit inflammatory response and apoptosis, and is also involved in RNA metabolism. In this study, we investigated the potential role of TNIP2 in amyloidogenesis critically associated with Alzheimer's disease (AD). We found a significant decline of ... TNIP2 protein level in both mouse and cell model of AD. In SH-SY5Y and HEK cells that stably express human full-length APP695 (SY5Y-APP and HEK-APP), TNIP2 overexpression decreased the protein levels of ?-secretase (BACE1) and C99, as well as A? peptides (including A?40 and A?42), while those of ?-secretase (ADAM10) and the related C83 remained unchanged. We further found that TNIP2 promoted the degradation of BACE1 mRNA and was able to bound to the 3' untranslated region (3'UTR) with the reduced luciferase activity. These results indicated that TNIP2 effectively inhibited amyloidogenic processing by regulating the 3'UTR-associated mRNA decay of BACE1.
Mesh Terms:
3' Untranslated Regions, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Aspartic Acid Endopeptidases, Humans, Mice, Mice, Transgenic, Neuroblastoma
3' Untranslated Regions, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Aspartic Acid Endopeptidases, Humans, Mice, Mice, Transgenic, Neuroblastoma
Neurosci Lett
Date: Jun. 21, 2023
PubMed ID: 37085111
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