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Did you know how priming factors help cancer cells grow and metastasize?
In the context of molecular biology, initiation factors are a type of protein that can bind to small subunit ribosomes during translation initiation, which is a key step in protein biosynthesis. Not only that, initiation factors can interact with inhibitory factors to slow down or prevent translation, or combine with activating factors to promote the initiation or acceleration rate of translation. In bacteria, these factors are simply called IFs (e.g., IF1, IF2, and IF3), whereas in eukaryotes they are called eIFs (e.g., eIF1, eIF2, eIF3).
The translation initiation process is usually described as three steps, and initiation factors play a crucial role in this process. First, the methionine-carrying tRNA binds to the small subunit ribosome, then to the mRNA, and finally to the large subunit ribosome. Each of these initiating factors that aid this process has a different role and structure.
Types of activation factors
Initiation factors are divided into three main categories according to their species. There are some homologies between these categories, as detailed in the different domain names.
Structure and function
Many domains have been conserved by evolution because prokaryotic initiation factors are structurally similar to eukaryotic factors. For example, the prokaryotic initiation factor IF3 contributes to initiation site specificity and binding to mRNA, which is functionally similar to the eukaryotic initiation factor eIF1.
The structure of eIF1 is similar to the C-terminal structure of IF3, both containing five β-strands and two α-helices.
In addition, IF1 and IF2 serve as eukaryotic homologs of eIF1A and eIF5B, and these factors also play an important role in the assembly of the initiation complex. eIF5B also contains an elongation factor whose Domain IV is closely related to the C terminus of IF2, both of which are composed of β-barrel structures.
The role of initiation factors in cancer
In cancer cells, the function of initiation factors is critical for cell transformation and tumor development. The survival and growth of cancer cells are directly related to the modification of initiation factors, and are also important targets for drug development. Cancer cells require more energy, which mainly comes from proteins. Overexpression of initiating factors is associated with the occurrence of various cancers. They increase the synthesis of proteins required by cancer cells.
The initiation factor eIF4E is particularly important for the synthesis of specific proteins that are critical in cancer cell proliferation and survival.
For example, eIF4E and its partners eIF4A and eIF4G play an important role in promoting the transformation of benign cancer cells into metastatic cancer cells. The largest initiation factor, eIF3, also plays an important role in human cancer due to its role in creating the 43S preinitiation complex, which successfully binds ribosomal subunits to mRNA.
Overexpression of eIF3 is closely related to various cancers such as breast, lung and colon cancer.
For example, eIF3c is a promoter that interacts with tumor suppressor proteins, and restriction of expression of certain eIF3 proteins has been shown to reduce cancer cell growth. The results of this study reveal an association between eIF3a and the early development of various tumors.
When the expression of eIF3a is inhibited, it has been shown to reduce the malignancy of breast and lung cancers, which may be related to its role in tumor growth. At different stages of cancer, the behavior and mechanisms of initiating factors may be regulated to adapt to the carcinogenic environment. This reveals priming factors as a new target for cancer research.
As we learn more about the role of priming factors in cancer, these factors may become central to future treatment strategies. Are you thinking about how to effectively apply this knowledge to improve the treatment outcomes for cancer patients?
