KAIST Uncovers Genetic Expression Regulation Principles in Cancer Development and Metastasis

Domestic researchers have identified the ‘core gene expression’ network of gene expression regulatory proteins involved in cancer occurrence and metastasis, opening up possibilities for developing therapeutic technologies.

KAIST announced on the 22nd that a joint research team led by Professors Kim Seyoon, Lee Kwangrok, and Cho Wonki from the Department of Biological Sciences has elucidated the core principles regulating gene expression in animal cells.

Group photo of Professor Kim Se-yoon's research team (first from the left). Photo by KAIST

The joint research team revealed that the IPMK protein, a key enzyme in the inositol metabolism system, acts as an important transcription activator in the core gene expression network of animal cells.

Inositol phosphate metabolites produced by inositol metabolic enzymes function as various secondary signaling molecules necessary for the signal transduction system of eukaryotic cells, broadly involved in cancer, obesity, diabetes, and neurological diseases.

The enzyme that plays a central role in the metabolic reactions of inositol, a nutrient known to be similar to glucose, is the IPMK protein (inositol polyphosphate multikinase), which has a direct function in regulating gene expression.

In particular, the IPMK enzyme has been reported to play an important role in the gene transcription process mediated by the serum response factor (SRF), a representative transcription factor in animal cells. However, until now, the actual mechanism of action was unknown.

The SRF transcription factor is a protein that directly regulates the expression of at least 200 to 300 genes, controlling animal cell growth, proliferation, apoptosis, cell motility, and playing an essential role in organ development such as the heart.

Based on this, the joint research team discovered that the IPMK protein directly binds to the SRF transcription factor. They also revealed that the IPMK protein alters the three-dimensional protein structure of the SRF transcription factor.

Furthermore, the transcription process of various genes is promoted through the SRF transcription factor activated by the IPMK enzyme, demonstrating that the IPMK protein serves as an essential regulatory switch to enhance the protein activity of the SRF transcription factor.

Based on this, the joint research team verified that if a problem occurs in the direct binding between the IPMK enzyme and the SRF transcription factor, the function and activity of the SRF transcription factor decrease, causing severe disruptions in gene expression.

In particular, by confirming that the intrinsically disordered region (IDR) of the SRF transcription factor is an important regulatory site, the study highlighted the biological significance of intrinsically disordered proteins.

Professor Kim Seyoon stated, “This research is significant in that it identified the IPMK protein, a key enzyme in the inositol metabolism system, as an important transcription activator in the core gene expression network of animal cells and presented the core mechanism to prove this. Through the research results, we expect to fundamentally understand various cancers derived from the SRF transcription factor, cancer metastasis phenomena, tissue differentiation and development from stem cells, and neural cell activation processes, thereby contributing to the future development of innovative therapeutic technologies.”

Meanwhile, this research was conducted with support from the Korea Research Foundation’s Mid-Career Research Program, Leading Research Center Support Project, Global Basic Research Laboratory Support Project, as well as the Seokyeongbae Science Foundation and Samsung Future Technology Development Program.

This content was produced with the assistance of AI translation services.