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Toporkiewicz, M.* ; Grzybek, M.* ; Meissner, J.* ; Michalczyk, I.* ; Dubielecka, P.M.* ; Korycka, J.* ; Seweryn, E.* ; Sikorski, A.F.*

Release of an ~55kDa fragment containing the actin-binding domain of β-spectrin by caspase-8 during FND-induced apoptosis depends on the presence of protein 4.1.

Arch. Biochem. Biophys. 535, 205-213 (2013)
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Analyses of the status of the membrane spectrin-based skeleton during fludarabine/mitoxantrone/dexamethasone-induced (FND-induced) apoptosis revealed proteolytic degradation of β-spectrin, with the prevalent appearance of a specific fragment with a molecular weight of ~55kDa, containing the actin-binding domain (ABD). Appearance of this fragment was dependent on induction of apoptosis. In silico proteolysis of spectrin identified caspase-8 as a candidate protease responsible for the generation of this ~55kDa ABD-containing fragment. Analyses of spectrin and procaspase-8 localization during early apoptosis indicated temporary (<30-120min) submembranous colocalization of both proteins. Proteolytic release of the N-terminal ~55kDa fragment of purified spectrin by recombinant caspase-8 does not occur in normal cells, but does occur in isolated membrane, such as red blood cell ghosts, or in vitro in the presence of apoptotic cell extracts. Surprisingly, proteolysis of purified spectrin by recombinant caspase-8 resulted in the generation of the ~55kDa fragment only in the presence of purified protein 4.1. This suggests that only the appropriate spatial arrangement of the spectrin-based membrane skeleton or the appropriate conformational state of spectrin, which are both known to be induced by 4.1, can sensitize β-spectrin to cleavage by caspase-8 at the N-terminal ABD-containing region.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0003-9861
e-ISSN 1096-0384
Zeitschrift Archives of Biochemistry and Biophysics
Quellenangaben Band: 535, Heft: 2, Seiten: 205-213 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)