Disrupted in renal carcinoma 2 (DIRC2), a novel transporter of the lysosomal membrane, is proteolytically processed by cathepsin L
01.10.2011
Savalas LR, Gasnier B, Damme M, Lübke T, Wrocklage C, Debacker C, Jézégou A, Reinheckel T, Hasilik A, Saftig P, Schröder B
Biochem J. 2011 Oct 1;439(1):113-28
DIRC2 (Disrupted in renal carcinoma 2) has been initially identified as a breakpoint-spanning gene in a chromosomal translocation putatively associated with the development of renal cancer. In the present study, lysosomal residence of overexpressed as well as endogenous DIRC2 was shown. Lysosomal targeting of DIRC2 was demonstrated to be mediated by a N-terminal dileucine motif. By disrupting this motif, DIRC2 can be redirected to the plasma membrane. DIRC2 is proteolytically processed into a N-glycosylated N-terminal and a non-glycosylated C-terminal fragment respectively. Proteolytic cleavage occurs in lysosomal compartments and critically depends on the activity of cathepsin L.
