Biomedical Engineering Reference
In-Depth Information
Metacaspases differ from caspases, however, in function and activity and
show different substrate specifi city to caspases. Two types of metacaspases
(type I or II) can be distinguished on the basis of presence or absence of a
prodomain, respectively (Bozhkov et al. 2010). Type I metacaspases have
an N-terminal extension reminiscent of the prodomain in initiator and
infl ammatory caspases. Type II metacaspases lack such a prodomain but
comprise a linker region between the assumed large and small subunits
(Uren et al. 2000, Vercammen et al. 2007). Structure predictions show
that they bear the core of the caspase/hemoglobinase fold, which is the
determining structural feature of all clan CD Cys proteases (Vercammen
et al. 2007). Only type I metacaspases are found in fungi, protozoa and
chromista while both type I and II are present in plants. This suggests
that type I metacaspases, caspases and paracaspases have a shared
ancestor originating from a possible horizontal gene transfer (HGT) event
between mitochondrial endosymbionts and host eukaryotic cells. Type II
metacaspases in turn may result from a second HGT occurrence during the
establishment of plastids from endosymbiotic cyanobacteria (Vercammen
et al. 2007).
Are Metacaspases caspases?
Many authors have questioned if metacaspases are in fact caspases
(Carmona-Gutierrez et al. 2010, Enoksson and Salvesen 2010, Vercammen
et al. 2007). There has been widespread deliberations regarding the
involvement of metacaspases in cell death after the discovery that
metacaspases have different cleavage specifi city than caspases; they
hydrolyze proteins after arginine or lysine (basic stress-induced PCD in
embryos of the Norway spruce (
Picea abies
), metacaspase mcII-Pa (type II
residues), and not after aspartate (an acidic residue). In fact, the omission
of metacaspases from the caspase family and their reordering into a
separate family in the CD clan of cysteine peptidases has been suggested
(Vercammen et al. 2007).
Assessment of the natural substrates of caspases and metacaspases
may reveal insight into the evolution of the programmed cell death
(PCD) machinery. The first biological substrate of metacaspases is
the phylogenetically conserved regulator of gene expression Tudor
staphylococcal nuclease (TSN). TSN is composed of a single Tudor
domain and fi ve staphylococcal nuclease-like domains and is vital for cell
viability (Sundstrom et al. 2009). During developmental and oxidative
metacaspase of
P. abies
) processes TSN at four sites containing either Arg
or Lys at P1 position and non conserved amino acid residues at P2, P3, and
P4. Human TSN is similarly cleaved but at a single site after aspartate at
