Characterization of an amyloid precursor protein-binding protein Fe65L2 and its novel isoforms lacking phosphotyrosine-interaction domains.

Human Fe65L2 is a member of the Fe65 protein family, which interacts with amyloid precursor protein (APP). Fe65L2 contains an N-terminal WW (Trp-Trp) domain followed by two phosphotyrosine-interaction domains, and consists of 486 amino acids. In the present study, we cloned and characterized two novel isoforms of Fe65L2, designated I-214 ...
and I-245, which are produced by alternative splicing of the RNA. The splicing events disrupt the ability to bind with APP and low-density-lipoprotein-receptor-related protein. Fe65L2 was highly expressed in the brain, whereas I-214 and I-245 were expressed in various tissues. In HEK-293 cells, Fe65L2 was expressed in the nucleus and cytosol, whereas I-245 and I-214 were localized exclusively to the nucleus. The ratio of I-214 to Fe65L2 mRNA was increased by apoptotic stimuli. Although the overexpression of either Fe65L2 or I-214 did not significantly affect the half-life and maturation of APP, or the secretion of secreted APP, the secretion of beta-amyloid peptide (Abeta)40 and Abeta42 was increased by overexpression of Fe65L2, but not by that of I-214. These results suggest that Fe65L2 affects Abeta production and a possible regulation of Fe65L2 function by alternative splicing.
Mesh Terms:
Alternative Splicing, Amyloid beta-Protein Precursor, Apoptosis, Carrier Proteins, Cell Line, Enzyme-Linked Immunosorbent Assay, Humans, Phosphoproteins, Polymerase Chain Reaction, Precipitin Tests, RNA, Messenger, Recombinant Proteins, Transcriptional Activation
Biochem. J.
Date: Nov. 01, 2002
Download Curated Data For This Publication
221644
Switch View:
  • Interactions 3