A MXXXL MOTIF CONFERING ENDOCYTOSIS OF BIOMOLECULES
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BACKGROUND: Endocytosis is an essential process in living cells that ensures proper regulation of the surface expression of membrane receptors and enzymes. This process is generally regulated by specific sequence motif in the cytoplasmic tail of internalizing proteins. The two major internalization motifs reported are tyrosine-based and di-leucine-based signals.
Prostate specific membrane antigen (PSMA), a potential therapeutic target and diagnostic marker, has been the subject of immense investigation due to its selective expression in human prostate cancer cells. Furthermore, PSMA over-expression is implicated in high-trade cancers and solid tumor formation.
INNOVATION: Like other membrane spanning proteins, PSMA expression is regulated by endocytosis. In studying the mechanism of internalization of PSMA, Rajasekaran et al reported that PSMA is internalized via a clathrin-dependent endocytic mechanism. This internalization is mediated by a cytoplasmic motif on PSMA having the sequence MXXXL. This motif can further be transferred to a non-internalizing protein TAC, which is the alpha-chain of interleukin 2-receptor. This signal peptide can therefore be used for conferring endocytosis of biomolecules.
APPLICATIONS:
1. Research use for:
DEVELOPMENT: UCLA researchers observed that the signal motif is required for PSMA internalization. Mutagenesis of N-terminal amino acid residues showed that position 1and 5 of the signal are required. The Tac-MXXXL fusion protein was shown to internalize like wild-type PSMA and is targeted to the recycling endosomal compartment.
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| Reference: UCLA Case No. 2004-275 |
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