Purification and cloning of aggrecanase-1: A member of the ADAMTS family of proteins

Tortorella MD; Burn TC; Pratta MA; Abbaszade I; Hollis JM; Liu R; Rosenfeld SA; Copeland RA; Decicco CP; Wynn R; Rockwell A; Yang F; Duke JL; Solomon K; George H; Bruckner R; Nagase H; Itoh Y; Ellis DM; Ross H; Wiswall BH; Murphy K; Hillman MC; Hollis GF; Newton RC; Magolda RL; Trzaskos JM; Arner EC

Science, Vol.284, No.5420, 1664-1666, 1999

DOI10.1126/science.284.5420.1664 Export Citation

Purification and cloning of aggrecanase-1: A member of the ADAMTS family of proteins

Tortorella MD, Burn TC, Pratta MA, Abbaszade I, Hollis JM, Liu R, Rosenfeld SA, Copeland RA, Decicco CP, Wynn R, Rockwell A, Yang F, Duke JL, Solomon K, George H, Bruckner R, Nagase H, Itoh Y, Ellis DM, Ross H, Wiswall BH, Murphy K, Hillman MC, Hollis GF, Newton RC, Magolda RL, Trzaskos JM, Arner EC

We purified,cloned, and expressed aggrecanase, a protease that is thought to be responsible for the:degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)] is a member of the: ADAMTS protein family that cleaves aggrecan at the glutamic acid-373-alanine-374 bond. The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.

Keywords:CARTILAGE PROTEOGLYCAN DEGRADATION;DROSOPHILA-MELANOGASTERCELLS;HUMAN SYNOVIAL-FLUID;INTERGLOBULAR DOMAIN;ARTICULAR-CARTILAGE;CLEAVAGE SITE;I REPEATS;THROMBOSPONDIN;CATABOLISM;ADHESION