A research team has discovered essential gene expression networks governed by specific proteins that fundamentally influence various biological processes, including cancer progression, metastasis, stem cell differentiation, and nerve activation.
A research team from KAIST has revealed the primary gene expression networks controlled by critical proteins that essentially drive biological phenomena like cancer development, metastasis, differentiation of tissues from stem cells, and neural activation. This finding paves the way for creating advanced therapeutic technologies.
On January 22nd, KAIST, led by President Kwang Hyung Lee, announced that a collaborative research effort by Professors Seyun Kim, Gwangrog Lee, and Won-Ki Cho from the Department of Biological Sciences has unveiled significant mechanisms that regulate gene expression in animal cells.
Inositol phosphate metabolites, generated by enzymes involved in inositol metabolism, act as crucial secondary messengers in eukaryotic cell signaling and are widely associated with conditions like cancer, obesity, diabetes, and neurological disorders.
The research team revealed that the inositol polyphosphate multikinase (IPMK) enzyme, a vital component of the inositol metabolic pathway, serves as a key transcriptional activator within the core gene expression networks of animal cells. Although IPMK had been previously recognized for its role in the transcription activity governed by the serum response factor (SRF)—a well-known transcription factor in animal systems—the exact mechanism of its function was not well understood until now.
SRF is a transcription factor that directly regulates the expression of 200-300 genes involved in cell growth, proliferation, apoptosis, and motility, making it essential for organ development, such as cardiac formation.
The research team found that IPMK interacts directly with SRF, modifying its three-dimensional structure. This interaction enhances the transcriptional activity of various genes facilitated by the SRF activated by IPMK, illustrating that IPMK functions as a vital regulatory switch to boost SRF’s protein effectiveness.
Moreover, the team confirmed that any disruption in the direct interaction between IPMK and SRF diminishes SRF’s functionality and activity, leading to severe gene expression issues.
By emphasizing the significance of the intrinsically disordered region (IDR) in SRF, the researchers highlighted the importance of intrinsically disordered proteins (IDPs). Unlike typical proteins that form distinct structures through folding, IDPs, including those with IDRs, lack specific shapes but carry out essential biological functions, garnering substantial interest in the scientific field.
Professor Seyun Kim remarked, “This study reveals an important mechanism showing that IPMK, a crucial enzyme in the inositol metabolic process, acts as a significant transcriptional activator in animal cell gene expression networks. By gaining insights into fundamental processes like cancer progression, metastasis, differentiation of stem cells, and neural activation via SRF, we anticipate that this discovery will facilitate the development of innovative therapeutic technologies.”
This research received support from the National Research Foundation of Korea’s Mid-career Research Program, Leading Research Center Program, and Global Research Laboratory Program, alongside funding from the Suh Kyungbae Science Foundation and Samsung Future Technology Development Program.
