Role in apoptosis

Peflin presents 40.9% identity with ALG-2. The protein has a long hydrophobic N-terminal extension containing nine nonapeptide repeats. Peflin is ubiquitously expressed. The function of peflin is still unknown, although recent experiments have shown a role in apoptosis. 

Acid CDase is localized in the lysosomes and it is suggested that it plays an important role in the catabolic pathway of sphingolipids. It has been also suggested recently, to play a role in apoptosis in response to TNFa induced death ofL929 cells (Strelow etal, 2000). 

Effector-induced SMase activation plays a highly pivotal role in apoptosis signaling since it has been described that the absence of CER generation, due to a defect in SMase stimulation, leads to cell resistance (for review see Eevade and Jaffrezou, 1999). However, the spacio-temporal organizahon of these events is unclear. SM, a major constituent of mammalian cell membranes, is found essentially within the plasma membrane and concentrated mostly in its outer leaflet. However, we and others have demonstrated that in response to cytotoxic effectors such as... 

The membrane-associated Akt kinase is now a substrate for protein kinase PDKl that phosphorylates a specific Thr and Ser residue of Akt kinase. The double phosphorylation converts Akt kinase to the active form. It is assumed that the Akt kinase now dissociates from the membrane and phosphorylates cytosolic substrates such as glycogen synthase kinase, 6-phosphofructo-2-kinase and ribosomal protein S6 kinase, p70 . According to this mechanism, Akt kinase regulates central metabolic pathways of the cell. Furthermore, it has a promoting influence on cell division and an inhibitory influence on programmed cell death, apoptosis. A role in apoptosis is suggested by the observation that a component of the apoptotic program. Bad protein (see Chapter 15) has been identified as a substrate of Akt kinase. 

At least ten caspases are known and many observations have confirmed their role in apoptosis (see also Chapter 32). In caspases 1 and 2 the side chains of Cys 285 and His 237 form the catalytic dyad and peptide NH groups of Cys 285 and Gly 238 form the oxyanion hole.333... 

The third MAP kinase pathway involving p38Mpk2 has a more ambiguous role in apoptosis. In some models it appears that inhibition of p38Mpk2 with SB203580 can suppress apoptosis [79] [86], but more often it has been found to have no role in apoptosis or cell survival. Furthermore, in some models, suppression of neither JNK nor p38Mpk2 appears to protect cells from apoptosis [86] [87], In most of these papers, attempts were made to inhibit only one of these pathways rather than inhibiting both pathways simultaneously, hence it is possible that both pathways may contribute in a redundant manner to the induction of apoptosis. 

Patel AJ, Lazdunski M (2004) The 2P-domain K+ channels role in apoptosis and tumorigenesis. Pflugers Arch 448 261-273... 

The mouse homologue, MFG-E8, plays a direct role in apoptosis as MFG — mice are defective in the phagocytosis of apoptotic cells by... 

Their opposing roles in apoptosis Susan Pyne... 

Chakravarthy BR, Walker T, Rasquinha I, Hill IE, MacManus JP. 1999. Activation of DNA-dependent protein kinase may play a role in apoptosis of human neuroblastoma cells. J... 

CD20 has a role in apoptosis, and binding of the antibody stimulates apoptosis. This means that even without recruitment of complement or ADCC antibodies can trigger a cytotoxic effect. 

Proteolysis plays a central role in apoptosis, as it does in the control of the cell cycle (Chapter 12). Apoptotic signals activate a cascade of proteolytic enzymes which degrade... 

The strategy used by the cysteine proteases is most similar to that used by the chymotrypsin family. In these enzymes, a cysteine residue, activated by a histidine residue, plays the role of the nucleophile that attacks the peptide bond (see Figure 9.18). in a manner quite analogous to that of the serine residue in serine proteases. An ideal example of these proteins is papain, an enzyme purified from the fruit of the papaya. Mammalian proteases homologous to papain have been discovered, most notably the cathepsins, proteins having a role in the immune and other systems. The cysteine-based active site arose independently at least twice in the course of evolution the caspases, enzymes that play a major role in apoptosis (Section 2.4.3). have active sites similar to that of papain, but their overall structures are unrelated. 

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