Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: A role for the IAPs

The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family

“…A recent study has shown that BID is activated through cleavage by caspase-2 during ER stress, and that BID null MEFs display significant resistance to ER stress (Upton et al, 2008). This finding is consistent with previous studies pointing to a role for BID in caspase-2-mediated cytochrome c release and to the involvement of BID and caspase-2 in ER stress-mediated apoptosis (Dahmer, 2005;Gao et al, 2005;Cheung et al, 2006;Murakami et al, 2007). Although the mechanism of caspase-2 activation during ER stress is unclear, there is evidence that it is independent of ER-localized BAX/BAK, but potentially dependent on BCL-2/BCLxL inhibitable activation of JNK (Murakami et al, 2007).…”

“…Like other initiator caspases, procaspase-2 is activated through dimerization followed by autocatalytic cleavage (Baliga et al, 2004). On the basis of the localization of a subpopulation of procaspase-2 at the ER in healthy cells (Cheung et al, 2006), it is tempting to speculate that caspase-2 activation in response to ER stress may be mediated through induced proximity as a result of recruitment to a signaling platform, possibly dependent, either directly or indirectly, on active JNK.…”

The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress

“…In fact, significant amounts of cellular c-ABL are located at the ER, and possibly upon PKCδ-mediated phosphorylation translocate to mitochondria (Ito et al, 2001;Qi and Mochly-Rosen, 2008). Also, Golgi/ER-located caspase-2 has been implicated in initiating ER-stress-induced apoptosis (Cheung et al, 2006). The mechanism of caspase-2 activation by ER stress has not been resolved, but there is evidence that caspase-2 activates the intrinsic apoptotic pathway, possibly by cleaving BCL-2 homology domain 3 (BH3)-only protein BID (Gu et al, 2008;Upton et al, 2008).…”

Metabolic Control of Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII)-mediated Caspase-2 Suppression by the B55β/Protein Phosphatase 2A (PP2A)

“…Multiple studies have implicated caspase-2 in cell stress-induced apoptosis (i.e. via DNA damage, endoplasmic reticulum stress, or heat shock) (1)(2)(3)(4)(5). Acting upstream of mitochondria in the intrinsic pathway (6), caspase-2 leads to cleavage of the pro-apoptotic Bcl-2 family member, Bid, to promote mitochondrial outer membrane permeabilization (7,8).…”

“…Specifically, we identify two novel sites of CaMKII phosphorylation (Thr 393 /Ser 395 on the Xenopus ␥ isoform L subunit and Thr 371 /Ser 373 on the human homolog) located within the association domain, whose phosphorylation falls in * This work was supported, in whole or in part, by National Institutes of Health Grant RO1 GM080333. 1 To whom correspondence may be addressed. Tel.…”