The dsRNA-dependent protein kinase, PKR and cell death

Attenuation of muscle atrophy in a murine model of cachexia by inhibition of the dsRNA-dependent protein kinase

“…Differences from NTB control are shown as a: Po0.05 or c: Po0.001, whereas differences from the solvent control are indicated as f: Po0.01. of PKR in mammalian and insect cells results in inhibition of cellular growth, which probably involves repression of translation through inhibition of the eIF2a pathway (Barber, 2005), whereas the expression of catalytically inactive dominant-negative PKR molecules causes the transformation of immortalised cells (Koromilas et al, 1992). Thus, inhibition of PKR phosphorylation might be expected to stimulate tumour growth.…”

C/EBP Homology Protein (CHOP) Interacts with Activating Transcription Factor 4 (ATF4) and Negatively Regulates the Stress-dependent Induction of the Asparagine Synthetase Gene

“…The transcription factor ATF4 is translationally induced by many stress conditions, such as amino acid deprivation (43), ER stress (45), the presence of long double-strand RNA (46), and heme deficiency (47). ATF4 is the functional ortholog of the yeast transcription factor GCN4, which is thought to be a "master regulator" of genes responsive to nutrient deprivation in yeast (48).…”

Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

“…PKR is activated by binding to double-stranded RNA formed during viral replication; it phosphorylates the a-subunit of translation factor eIF2, resulting in inhibition of protein synthesis (Barber, 2005;Garcia et al, 2007). PKR has also been implicated in many additional cellular stress responses and corresponding signal transduction pathways, including the nuclear factor-kB and p38-mitogen-activated protein kinase pathways (reviewed by Barber, 2005;Garcia et al, 2006Garcia et al, , 2007. A major role for PKR has recently emerged in the control of apoptosis, following activation of the tumour-suppressor p53 pathway (Yoon et al, 2009).…”