Detection of a secreted metalloprotease within the nuclei of liver cells

• DOI: 10.1039/c0mb00303d
• Publication Date: 2011-04-11T13:05:03Z
• Authors: Ryan C. Hunt; S. Geetha; Courtni E. Allen; Klilah Hershko; Robert Fathke; Philip L. Kong; Elizabeth Plum; Evi Budo Struble; Kenji Soejima; Scott Friedman; Susan Garfield; S. Balaji; Chava Kimchi-Sarfaty
• Keywords: Cell Nucleus; Models, Molecular; 0301 basic medicine; ADAMTS13 Protein; Protein Sorting Signals; Protein Structure, Secondary; Cell Line; ADAM Proteins; 03 medical and health sciences; Sequence Analysis, Protein; Hepatocytes; Humans; Protein Interaction Domains and Motifs; Amino Acid Sequence; Conserved Sequence

ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the secretory system, detected an appreciable level endogenous within nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present propeptide may act as nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly potentiated localization. Bioinformatics analysis suggests that CUB-2 domain has double-stranded beta helix (DSBH) structural architecture characteristic protein–protein interaction modules like nucleoplasmins, class I collagenase, tumor necrosis factor ligand superfamily, supernatant protein (SPF) B1 neuropilin-2. Based on contextual evidence largely conserved polar residues could be mapped template CUB homolog, hypothesize might involved