Cellular localization of MAGI-1 caspase cleavage products and their role in apoptosis.
MAGI-1 is a membrane-associated guanylate kinase (MAGUK) protein present at adherent and tight junctions, where it acts as a structural and signaling scaffold. During apoptosis, MAGI-1 is cleaved by caspases at Asp761 into N- and C-terminal cleavage products, allowing further dismantling of the cell junctions, one of the key features of apoptosis. Here, we investigated the cellular distribution and possible proapototic role of MAGI-1 caspase cleavage products. Full-length MAGI-1 exhibited submembrane localization, while the N-terminal caspase cleavage product of MAGI-1 is translocated to the cytosol and the C-terminal caspase cleavage product accumulates in the nucleus. When overexpressed in MDCK cells, both N- and C-terminal MAGI-1 caspase cleavage products exhibited minor proapoptotic activity, although their role in apoptosis is probably more passive.
Ivanova
Saska
S
Department of Biochemistry, Molecular and Structural Biology, J Stefan Institute, SI-1000, Ljubljana, Slovenia.
Repnik
Urska
U
Banks
Lawrence
L
Turk
Vito
V
Turk
Boris
B
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D004285:Dogs; D051528:Guanylate Kinases; D006801:Humans; D006868:Hydrolysis
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D051528:Guanylate Kinases; C113338:MAGI1 protein, human; D020169:Caspases