Initiation factor

The initiation factors are divided into three major groups by taxonomic domains. There are some homologies shared (click the domain names to see the domain-specific factors): == Structure and function ==

Many structural domains have been conserved through evolution, as prokaryotic initiation factors share similar structures with eukaryotic factors. also showing the Shine-Dalgarno sequence upstream of the start codon A eukaryotic initiation factor eIF3 plays an important role in translational initiation. It has a complex structure, composed of 13 subunits. It helps to create the 43S pre-initiation complex, composed of the small 40S subunit attached to other initiation factors. It also helps to create the 48S pre-initiation complex, consisting of the 43S complex with the mRNA. The eIF3 factor can also be used post-translation in order to separate the ribosomal complex and keep the small and large subunits apart. The initiation factor interacts with the eIF1 and eIF5 factors used for scanning and selection of the start codons. This can create changes in the selection of the factors, binding to different codons. Another important eukaryotic initiation factor, eIF2, binds the tRNA containing methionine to the P site of the small ribosome. The P site is where the tRNA carrying an amino acid forms a peptide bond with the incoming amino acids and carries the peptide chain. The factor consists of an alpha, beta, and gamma subunit. The eIF2 gamma subunit is characterized by a GTP-binding domain and beta-barrel folds. It binds to the tRNA through GTP. Once the initiation factor helps the tRNA bind, the GTP hydrolyzes and is released the eIF2. The eIF2 beta subunit is identified by its Zn-finger. The eIF2 alpha subunit is characterized by an OB-fold domain and two beta strands. This subunit helps to regulate translation, as it becomes phosphorylated to inhibit protein synthesis. == In cancer ==

In cancerous cells, initiation factors assist in cellular transformation and development of tumors. The survival and growth of cancer is directly related to the modification of initiation factors and is used as a target for pharmaceuticals. Cells need increased energy when cancerous and derive this energy from proteins. Over-expression of initiation factors correlates with cancers, as they increase protein synthesis for proteins needed in cancers. Some initiation factors, such as eIF4E, are important in synthesizing specific proteins needed for the proliferation and survival of cancer. The careful selection of proteins ensures that proteins that are usually limited in translation and only proteins needed for cancer cell growth will be synthesized. This includes proteins involved in growth, malignancy, and angiogenesis. The eIF4E factor, along with eIF4A and eIF4G, also play a role in transitioning benign cancer cells to metastatic. The largest initiation factor, eIF3, is another significant initiation factor in human cancers. Due to its role in creating the 43S pre-initiation complex, it helps to bind the ribosomal subunit to the mRNA. The initiation factor has been linked to cancers through over-expression. For example, one of the thirteen eIF3 proteins, eIF3c, interacts with and represses proteins used in tumor suppression. Limited expression of certain eIF3 proteins, such as eIF3a an eIF3d, has been proven to decrease the vigorous growth of cancer cells. The over-expression of eIF3a has been linked to breast, lung, cervix, esophagus, stomach, and colon cancers. It is prevalent during early stages of oncogenesis and likely selectively translates proteins needed for cell proliferation. When eIF3a is suppressed, it has shown to decrease the malignancy of breast and lung cancer, most likely due to its role in tumor growth. == See also ==