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  • On the other hand the


    On the other hand, the death domain is a conserved stretch of around 80AA which is commonly found in death receptor proteins, it play a major role in the interaction between other proteins. Also as a platform for the death-inducing signaling complex (DISC) formation (Chaigne-Delalande et al., 2008). The serine rich C-terminal tail of DAPK1 plays a negative feedback to the putative function of the death domain (Feinstein et al., 1995) (Fig. 1). The kinase domain of DAPK1 is required for its cell killing activity (Shiloh et al., 2014). However, the death association domain is important for Caspase-2 Colorimetric Assay Kit fulfilling the function. The cytoskeleton and ankyrin repeats domains are thought to be involved in the subcellular targeting of DAPK1 (Cohen et al., 1999). The multi-domain structure of DAPK1 and its participation in various apoptotic systems imply that the protein may interact with wide range of intracellular components to exert its action (Fig. 1).
    DAPK1 induced pathways It has been for almost twenty years an unsettling debate whether DAPK1 is a pro- or anti-apoptotic kinase. Multiple studies have shown the involvement of DAPK1 in multiple processes of cell growth like Caspase-2 Colorimetric Assay Kit check points (Gade et al., 2016), apoptosis, and autophagy. The execution of cell death by DAPK1 takes place in response to various stimuli such as death receptor activation, cytokines, matrix detachment, ceramide3 and others (Bajbouj et al., 2009; Cohen et al., 1999, 1997; Deiss et al., 1995; Inbal et al., 1997; Jang et al., 2002; Yamamoto et al., 2002). It has been suggested that the role of DAPK1 is associated with both types of cell death apoptosis and autophagy which they are respectively caspase-dependent and caspase-independent cell death (Galluzzi et al., 2018). DAPK1 acts as a critical component in the ER stress-induced cell death pathway (Gade et al., 2014). In addition, genetic engineering techniques was used to overexpress the wild type or mutant forms of DAPK1 in mouse demonstrated the pro-apoptotic function of DAPK1 (Farag and Roh, 2018; Shohat et al., 2001). However, many other studies showed that the over-expression of DAPK1 does not induce a caspase-dependent apoptosis under normal growth conditions (Jin et al., 2001). It has been suggested that, depending on particular cell types, the response to specific apoptosis inducers can vary and DAPK1 can either promote (Chen et al., 2005; Cohen et al., 1999) or antagonize apoptosis (Jin et al., 2002, 2001).
    DAPK1 in the nervous system It has been shown the abundance of the mRNA levels of DAPK1 in adult brain (Bialik and Kimchi, 2004). DAPK1 expression decreased remarkably in the brain after birth, limiting it to restricted mature neuronal populations such as olfactory bulb, hippocampal formation, cerebellar Purkinje and granule cells (Sakagami and Kondo, 1997; Tian et al., 2003; Yukawa et al., 2004). This was based on the analysis of patterns of DAPK1 expression where DAPK1 mRNA was initially observed at embryonic day 13 (E13) and was thereafter, detected throughout the entire embryonic period (Yamamoto et al., 1999). It has also appeared in the mantle and ventricular zones of the entire neuraxis in the early stages of brain formation. This differentially regulated expression of DAPK1 during development and its restricted expression in mature neuronal population indicate that DAPK1 might be involved in some neuronal functions besides executing the developmental neuronal programmed cell death (Sakagami and Kondo, 1997). DAPK1 has been suggested to have other functional roles such as regulating exocytosis of neurotransmitter release by phosphorylation of syntaxin-1 (Tian et al., 2003) and protecting neurons during development or recovery from hypoxic-ischemic injury (Schumacher et al., 2002). Moreover, DAPK1 has been shown to function as a mediator of multi-types of stress signals induced by deprivation of neuronal cells from Netrin-1, and stimulation of N-methyl-D-aspartate receptor (NMDA) receptors in cerebral ischemia (Bialik and Kimchi, 2010).