Arrest release factors

Termination and release of the protein from the ribosome requires the presence of a stop codon and the protein release factors. However, protein synthesis can also come to a halt if there is not enough of one of the amino acids bound to tRNA. In this case, the growing peptide chain is not released from the ribosome, but remains, in arrested development, until the required amino acyl tRNA is available. This means that if the intake of one of the essential amino acids is inadequate then, once supplies are exhausted, protein synthesis will come to a halt. 

Figure 26.1 Immortalization of human cells Cells enter replicative senescence at mortality stage 1 (Ml Hayflick limit) after about 60 population doublings (PD). The protein p 16 accumulates in senescent cells. The simian virus 40 (SV40) large T antigen as well as the human papilloma virus (HPV) type 16-E6 and E7 proteins sequester the retinoblastoma protein (Rb) and/or p53 constitutively releases the transcription factor E2F. E2F induces expression proteins required for progression through Gl/S transition, thus the cells escape cell cycle arrest. At mortality stage 2 (M2), transformed cells must overcome senescence and crisis before they are immortalized. This is likely to involve the activation of telomerase either by the introduction of hTERT cDNA or by a genetic change that activates telomerase.

Liu, J. and Mailer, J. L., 2005, Calcium elevation at fertilization coordinates phosphorylation of XErpl/Emi2 by Plxl and CaMK II to release metaphase arrest by cytostatic factor, Curr Biol, 15, pp 1458-68. 

In 1991 inhibition of PKC activity was found to be at the basis of the vascular smooth muscle cell growth arrest induced by a-tocopherol [16,17]. A number of reports have subsequently confirmed the involvement of PKC in the effect of a-tocopherol on different cell types, including monocytes, macrophages, neutrophils, fibroblasts and mesangial cells [8,18-20]. a-Tocopherol, but not P-tocopherol, was found to inhibit thrombin-induced PKC activation and endothelin secretion in endothelial cells [21]. a-Tocopherol, and not P-tocopherol or trolox, inhibits the activity of PKC fi-om monocytes, followed by inhibition of phosphorylation and translocation of the cytosolic factor p47(phox) and by an impaired assembly of the NADPH-oxidase and of superoxide production [22]. a-Tocopherol has the important biological effect of inhibiting the release of the proinflammatory cytokine, IL-lp, via inhibition of the 5-lipoxygenase pathway [23]. 

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