Insulin-like Growth Factor 2 mRNA Binding Protein 1, or IGF2BP1, is a protein that plays a widespread role in various biological processes within the human body. Understanding this protein offers insights into fundamental cellular operations and how they can go awry in disease.
Understanding IGF2BP1
IGF2BP1 is an RNA-binding protein (RBP), meaning it directly interacts with RNA molecules within cells. It belongs to the IGF2BP family, which includes IGF2BP1, IGF2BP2, and IGF2BP3.
These proteins are highly conserved across different species, highlighting their fundamental importance in biology. IGF2BP1 is primarily found in the cytoplasm, where it associates with target messenger RNAs (mRNAs) in specialized structures called cytoplasmic ribonucleoprotein complexes (mRNPs). While predominantly cytoplasmic, IGF2BP1 has also been observed in the nucleus in certain cell types, such as spermatogenic cells.
How IGF2BP1 Influences Cellular Processes
IGF2BP1’s primary function involves binding to specific messenger RNA (mRNA) molecules, thereby regulating their fate within the cell. This binding allows IGF2BP1 to influence several post-transcriptional processes, including mRNA stability, translation, and localization. By controlling these aspects, IGF2BP1 ultimately impacts gene expression and the production of proteins.
One way IGF2BP1 exerts its influence is by “caging” target transcripts into mRNPs, which facilitates their transport and temporary storage within the cytoplasm. This mechanism also helps control where and when these mRNAs encounter the cellular machinery responsible for protein synthesis. IGF2BP1 can also shield target mRNAs from degradation by enzymes called endonucleases or from being targeted by microRNAs.
For example, IGF2BP1 regulates the localized translation of beta-actin (ACTB) mRNA, a process important for cell polarity, movement, and the formation of nerve cell extensions. IGF2BP1 initially associates with ACTB mRNA in the nucleus, and the resulting complex is then transported along the cell’s internal scaffolding to the cell periphery. During this transport, IGF2BP1 can prevent ACTB mRNA from being translated; however, upon reaching its destination near the cell membrane, IGF2BP1 can be modified, allowing the mRNA to be released and protein synthesis to begin. These actions collectively contribute to fundamental cellular processes such as cell growth, proliferation, and differentiation.
IGF2BP1’s Impact on Development and Disease
IGF2BP1 plays a role in embryonic development, organ formation, and tissue development. Its presence is particularly high during the early stages of development, from the zygote to the embryo, and its expression is substantially reduced in most normal adult tissues. Studies in various organisms have shown IGF2BP1 expression in different developmental cell types.
The protein’s proper regulation is important for normal development; for instance, mice lacking IGF2BP1 exhibit characteristics like dwarfism, reduced survival rates, and abnormal intestinal development, with a substantial percentage experiencing perinatal mortality. Its influence extends to various diseases, particularly cancer, where it often acts as a proto-oncogene. IGF2BP1 is frequently re-expressed in aggressive cancer types and its elevated levels are associated with poor patient outcomes.
In cancer, IGF2BP1 promotes tumor growth, spread, and resistance to therapies by stabilizing and translating messenger RNAs that encode proteins involved in cancer progression. For example, it contributes to the growth of liver, breast, and colorectal cancers. Specifically, IGF2BP1 has been shown to promote the proliferation and invasion of esophageal squamous cancer cells by stabilizing INHBA mRNA, leading to increased protein expression and activation of signaling pathways that drive malignant characteristics. Furthermore, IGF2BP1 can affect tumor metabolism, including glycolysis and lipid metabolism, which allows cancer cells to adapt to harsh environments. Beyond cancer, IGF2BP1 has also been linked to metabolic disorders and certain hematological diseases. Given its widespread involvement in disease, IGF2BP1 is being explored as a potential biomarker for prognosis and a target for new therapeutic approaches in cancer.