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Signal transduction and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Brendan Egan, Adam P. Sharples
While all three processes are tightly regulated, the rate-limiting step for translational control occurs at the initiation step. Translation initiation is a multi-step process regulated by eukaryotic initiation factors (eIFs) and culminates in formation of the 80S initiation complex. Prior to translation, the subunits of the ribosome are separate and the 40S subunit must be ‘primed’ by binding of a transfer RNA (tRNA). The tRNA contains the complementary sequence for the AUG start codon of mRNA and is also attached to the amino acid methionine. Proteins are synthesised beginning from the amine N-terminal and ending with a carboxyl C-terminal; therefore, all proteins begin with a methionine residue, although this is often removed after translation. The priming of the 40S ribosome is regulated in part by eIF3 and creates a 43S pre-initiation complex. Next eIF4 guides the 5’-end (named 5’-cap) of mRNA into the 43S complex and the ribosome proceeds along the mRNA until the start codon is found. Other eIFs then recruit the 60S subunit to create the 80S initiation complex, and synthesis of the polypeptide chain begins.
Protein and amino acids
Published in Jay R Hoffman, Dietary Supplementation in Sport and Exercise, 2019
The EAAs play a role in regulating MPS by enhancing the efficiency of translation (34) due to a stimulation of peptide chain initiation relative to elongation (40). Peptide-chain initiation involves dissociation of the 80S ribosome into 40S and 60S ribosomal subunits, formation of the 43S preinitiation complex with binding of initiator methionyl-tRNA to the 40S subunit, binding of mRNA to the 43S preinitiation complex and association of the 60S ribosomal subunit to form an active 80S ribosome (74). First, peptide chain initiation is controlled by the binding of initiator methionyl tRNA to the 40S ribosomal subunit to form the 43S preinitiation complex, a reaction mediated by eukaryotic initiation factor 2 (eIF2) and regulated by eIF2B. Second is the binding of mRNA to the 43S preinitiation complex, which is mediated by eIF4F (73). During translation initiation, the eIF4E·mRNA complex binds to eIF4G and eIF4A to form the active eIF4F complex (63). The binding of eIF4E to eIF4G is controlled by 4E-binding protein 1 (4E-BP1), a repressor of translation. Binding of 4E-BP1 to eIF4E limits eIF4E availability for formation of active eIF4E·eIF4G complex and is regulated by phosphorylation of 4E-BP1 (73).
Mechanisms of Hepatitis C Virus Clearance by Interferon and Ribavirin Combination
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Srikanta Dash, Partha K. Chandra, Kurt Ramazan, Robert F. Garry, Luis A. Balart
The mechanism of IFN-α antiviral activity through inhibition of HCV IRES–mediated translation is supported by a number of studies (Kato et al. 2002; Koev et al. 2002; Rivas-Estillas et al. 2002; Shimazaki et al. 2002; Wang et al. 2003; Dash et al. 2005). The newly discovered type III IFN, called IFN-λ, also inhibits IRES-mediated translation of HCV and hepatitis A (Kanda et al. 2012). There is an agreement among many studies indicating that type I, type II, and type III IFNs inhibit HCV replication by blocking HCV IRES–mediated translation that involves the PKR-induced phosphorylation of eIF2α. The eIF2α is a eukaryotic initiation factor required for protein translation (Dabo and Meurs 2012). This eIF2 protein exists as heterodimer consisting of eIFα, eIFβ, and eIFγ. The eIF2 protein complexes with GTP and initiator t-RNA to form the 43S preinitiation complex. The 43S preinitiation complex binds to an AUG codon on the target mRNA to initiate protein translation. The dissociation of the complex occurs when the eIF2’s GTP is hydrolyzed by eIF5 (a GTPase-activating protein). The conversion causes eIF2-GDP to be released from the 48S complex, allowing translation to begin after recruitment of a 60S ribosome subunit and formation of 80S initiation complex. With the help of guanine nucleotide exchange factor eIF2-β, the eIF2-GDP is converted eIF2-GTP, which initiates another round of translation. The phosphorylation of eIF2α inhibits recycling of this initiation factor and blocks protein synthesis.
The Prognostic Significance of EIF3C Gene during the Tumorigenesis of Prostate Cancer
Published in Cancer Investigation, 2019
Jianxin Hu, Heng Luo, Yuangao Xu, Guangheng Luo, Shuxiong Xu, Jianguo Zhu, Dalong Song, Zhaolin Sun, Youlin Kuang
Protein translation is a critical process throughout the lifetime of cells. This process consists of three steps: initiation, elongation, and termination. It is shown that eukaryotic initiation factor 3 (eIF3) is required for initiation of protein translation and acts as a docking site for the formation of 43S preinitiation complex (PIC) which is consisted of Met-tRNAiMet, eIF2, and 40S ribosomal subunit (7, 8). Then with the help of eIF4F, eIF4B, and PABP, eIF3 promotes the interaction of 43S PIC with the 5-terminal of capped mRNA followed by formation of 48S PIC. In 48S PIC, eIF3 facilitates the AUG recognition on mRNA (9). EIF3C, composed of 913 amino acids, is one of the 13 subunits of eIF3 factor. EIF3C is highly conserved in evolution and constitutes the function core of eIF3 with other five subunits (10). EIF3C plays a very important role during development and homeostasis. For example, decreased EIF3C disrupted the AUG recognition of 48S PIC and resulted in inefficiency of translation (7). The mice phenotype extra-toes spotting could be attributed to mutations in EIF3C (11). EIF3C gene is located on chromosome 16p11.2, which is an unstable region in the genome. Overexpression of EIF3C gene was reported to be associated with many types of cancers (12). For example, high expression of EIF3C showed adverse effects on tumor suppressor neurofibromatosis 2(NF2) and induced cancer cell proliferation (13). Forced expression of EIF3C promoted proliferation of glioma cells (14, 15). In contrast, knockdown of EIF3C reduced the survival of colon cancer cells by inhibiting the proliferation and colony formation of tumor cells (16). EIF3C was also found to be critical for survival of MCF-7, B16F10, and HeLa cells (17). However, there is no study about the role of EIF3C in PCa.